Mark of Cain
Cain: The Mark can be transferred to someone who's worthy.
Dean: You mean a killer like you?
Cain: Yes. But you have to know with the Mark comes a great burden. Some would call it a great cost.
Cain: Yes.
Dean: Can I use it to kill that bitch?
– Cain and Dean, 9.11 First Born
History
The Mark of Cain is a brand placed on Cain by Lucifer. It is the source of the First Blade's power. The Mark and the Blade work together, and without it the First Blade is rendered useless. The Mark can also be transferred if the person is "worthy of it"; which is unspecified, but may mean being a killer, or something else. According to Cain, taking on the Mark comes with a great cost and burden. According to Rowena, it is simply a curse, the first curse in existence.
After Cain was given the Mark, he begins to realize what toll taking the Mark has taken on him, and rather than be controlled by his murderous compulsion, he attempts to kill himself with the First Blade. However the Mark would not let him die, and he was reborn a demon.
After gaining the Mark, Dean began to exhibit more aggressive behavior, and once the Mark was activated by the First Blade his aggression was amplified. Once he began killing with the First Blade, the burden of the Mark became apparent -- the more Dean kills the better he will feel, the less he kills the worse he will feel, and if he does not keep killing it will eventually cause his death. Because as Crowley informs Dean, the human body was never meant to contain the First Blade's power.
After Metatron kills him, Dean is resurrected by the power of the Mark and the First Blade. It has twisted his soul until it is demonic. Dean shows no care for anyone - even Sam. The Mark of Cain also causes Dean's body has been shown to be able to heal from the wounds inflicted on it. Crowley reveals to Dean that the Mark needs to be sated with killing, or Dean will become even darker.
Sam is able to cure him of being a demon, however, he still possesses the Mark. After seemingly unaffected by the Mark for months, its powers started to affect Dean again, giving him a precognitive nightmare of a massacre of humans he committed under its influence a few days later.
Unable to find any way in the lore to stop the Mark's influence, Castiel retrieves Metatron from his incarceration in Heaven. Metatron refuses to provide any information, however as Dean tortures him, Metatron says something about the "river ends at it's source". Sam suggests to Dean that he needs to find a power within himself to resist the influence of the Mark.
After killing Abaddon's demons, Cain fell back under the Mark's influence, deciding to slaughter his own descendants as he felt his bloodline was "tainted." To stop him, Dean, Sam, Castiel and Crowley teamed up together against the Father of Murder, imprisoning him in a devil's trap which limited his powers but didn't block them completely. After Cain was trapped, the two bearers of the Mark of Cain faced off in a fight to the death which Dean won, killing Cain who claimed that there was no cure for the Mark and that it eventually takes over you completely no matter how much you try to fight it.
Episodes
9.11 First Born
Knowing that Dean wants the First Blade to kill Abaddon, and after seeing him kill a number of demons, Cain decides that Dean is "worthy" of carrying the Mark in order to wield the blade. Cain transfers the mark to Dean, where it appears on his right forearm. Cain warns Dean that carrying the mark will come at a cost.
9.12 Sharp Teeth
Dean and Sam have parted ways, but meet up at a hospital when they both find out Garth has been hospitalised. While there, Dean tells Sam about getting the Mark of Cain.
9.13 The Purge
Dean tells Sam that his research hasn't yielded any more information about the Mark of Cain.
9.16 Blade Runners
Finding the First Blade in the possession of Magnus, Dean is given the Blade by Magnus who wants to keep Dean as part of his "collection" as he is the only one who can use it due to the Mark. The Mark glows when Dean holds the Blade and it affects him strangely until he drops the Blade. Magnus tells Dean that he will get used to the feeling in time.
After Dean kills Magnus with the Blade, the Mark affects him strangely until he drops the Blade again.
9.17 Mother's Little Helper
Dean is feeling the after effects of invoking the power of the Mark of Cain when he used the First Blade. He's not sleeping, is obsessed with finding Abaddon - to the point of refusing to accompany Sam on a hunting trip - and his hands are shaking. Crowley suggests that using the Blade made him feel powerful and virile - but also scared.
9.18 Meta Fiction
Dean rubs his arm once early in the episode, as though the mark is sore or bothering him. Towards the end of the episode, Castiel asks if Dean is okay, sensing something; then asks him, "Dean, what did you do?" Dean demurs but Castiel grabs Dean's arm and pulls up Dean's sleeve to reveal the mark. "Damn it, Dean!" Castiel says, but without further explanation. After Dean gets into the Impala, Castiel tells Sam to watch over Dean.
9.19 Alex Annie Alexis Ann
Dean is shown to be able to overpower the vampire Connor with little effort, and slowly decapitates him with the blunt edge of his knife, presumably because of the Mark of Cain. Sam comments that Dean seemed to enjoy the kill a bit too much.
9.21 King of the Damned
Dean faces off against Abaddon armed with the First Blade. During the fight, he is able to kill another demon with the Blade but is pinned to the wall by Abaddon with telekinesis. The Mark, glowing brightly, provides Dean with immunity to Abaddon's powers with great concentration, but it doesn't last and he's pinned to the wall again without the Blade. With concentration, Dean is able to summon telekinesis with the Mark's power and call the Blade into his hand. The Mark then grants Dean full immunity to Abaddon's powers and he is able to use the Mark and the Blade to finally kill her. The rage that comes with the Mark however causes him to stab Abaddon's corpse several times.
9.22 Stairway to Heaven
When Gadreel arrives at the Bunker looking to join with the Winchesters and Castiel in taking down Metatron, Dean approaches him after he has made his case and extends his hand to Gadreel. As the two shake hands, when Dean suddenly removes the First Blade from his jacket and slashes it across Gadreel's chest. Prompting Sam and Castiel to jump on Dean and hold him back as he consumed by bloodlust.
9.23 Do You Believe in Miracles?
Sam and Castiel are trying to restrain Dean after he has attacked and slashed Gadreel. They lock him in the dungeon, while Dean argues he is the only one who can kill Metatron, Sam warns that the Mark of Cain is affecting him. Sam and Castiel leave, locking Dean inside.
When Dean begins throwing up blood, he manages to find the ingredients for a spell, and summons Crowley. Crowley informs Dean that the Mark of Cain will drive him to kill more and more - and that if he doesn't, he will die. Dean protests out that Cain was still alive, but Crowley points out that Cain was a demon, not a human, and that human bodies aren't meant to contain that kind of power. Dean then asks Crowley to help him get the First Blade and escape.
During Dean's confrontation with Metatron, Dean becomes mortally wounded, and soon dies in Sam's arms. Sam brings Dean's body back to the Bunker and lays him out in his room, while contemplating his next move, ultimately deciding to summon Crowley to fix the mess he believes Crowley caused.
However Crowley is already in Dean's room. He begins speaking to Dean's dead body, telling him that he didn't know the full extent of the Mark of Cain. "It's important," he says, that Dean knows he didn't lie. He does say that he omitted to tell Dean that Cain also did not want to become the killer the Mark was making him -- so he stabbed himself with the First Blade. He tells him how Cain's suicide failed, because the Mark wouldn't let him die.
Crowley then places the First Blade into Dean's hand. He tells Dean that he's feeling a new kind of life and tells him to open his eyes. He tells Dean he will now see what he sees, and feel what he feels.
After a moment, Dean's eyes open, which have become a demonic black.
10.01 Black
Now resurrected, the power of the Mark has twisted Dean's soul making him a demon. Dean shows no care for anyone -- even Sam. Crowley tells Dean that he has been sending Abaddon loyalists to him to keep him and sharp and because the Mark needs to be sated with killing, or the Mark's bloodlust will consume Dean even more.
10.02 Reichenbach
In order to feed the Mark, Crowley sends Dean to kill Lester Morris' wife after he makes a deal to kill her due to her cheating. Dean agrees, but kills Lester instead as he discovers that Lester cheated first and is a scumbag.
10.03 Soul Survivor
Despite the Mark, Sam is able to cure Dean of being a demon, however, the Mark's power causes Dean to retain demon mannerisms long into the cure and try to kill Sam before being stopped by Castiel. As Castiel points out, while Dean is no longer a demon, he still has a Mark and that will eventually become a problem.
10.06 Ask Jeeves
After Dean unloads several unnecessary shots into the shapeshifter Olivia after killing her, Sam suggests that its the effects of the Mark, but Dean denies it.
10.08 Hibbing 911
Searching through the Men of Letters files, Sam and Dean find nothing on the Mark to Dean's frustration.
After killing two vampires, Dean tells Sam that for the first time it felt like the Mark wasn't pushing him to kill that he was himself again, something that relieves them both. Afterwards, he rubs the Mark through his jacket sleeve.
10.09 The Things We Left Behind
Dean receives what is later revealed to be a precognitive nightmare, presumably from the Mark of him in a room holding a knife and surrounded by dead bodies. After being attacked by a loan shark and his thugs, Dean falls under the Mark's influence once more and brutally slaughters the loan shark, his men and Randy, making his nightmare come true.
10.10 The Hunter Games
As Dean begins beating on and torturing Metatron for information on removing the Mark of Cain, the Mark begins to react. Metatron also reveals that the more Dean succumbs to the violent urges, the deeper under the Mark's spell he becomes.
Unable to find any way in the lore to stop the Mark's influence, Castiel retrieves Metatron from his incarceration in Heaven. Metatron refuses to provide any information, however as Dean tortures him, Metatron says something about the "river ends at it's source"". Sam suggests to Dean that he needs to find a power within himself to resist the influence of the Mark.
Soon after Dean is attacked by some thugs, he and does find he can stop himself from killing - this time.
10.11 There's No Place Like Home
Sam and Dean continue their research into the Mark and Sam finds a lore book, The Book of the Damned that might have something and Charlie Bradbury agrees to check it out, dedicating herself to helping rid Dean of the Mark since she can't return to Oz.
10.12 About a Boy
Dean locks himself in his room in the Men of Letters Bunker for a week researching the Mark. Eventually Sam manages to get him to leave and work a case with him in Pendelton, Oregon.
When Dean gets transformed into a teenager by Hansel, he no longer has the Mark as he didn't have it as a teenager. As a result, he suggests remaining as a teenager as a solution, but is forced to reverse the spell to save Sam. The Mark returns when Dean becomes an adult again.
10.13 Halt & Catch Fire
In hopes of finding a cure for the Mark, Castiel is working to track Cain, believing he may have the answers.
After stopping the ghost of Andrew Silver, Dean decides that while he will never stop fighting the Mark, he is going to give up hope on looking for a cure.
10.14 The Executioner's Song
Cain has fallen back under the Mark's influence and began killing again following his slaughter of Abaddon's demons. Feeling that his bloodline is "tainted", Cain decides to kill them all and begins hunting down entire families descended from him to eliminate. After finding this out, Sam, Dean, Castiel and Crowley team up together to bring Cain down once and for all, hoping to learn a cure from him in the process. They manage to capture Cain in a devil's trap, but he claims there is no cure and its better to just give in to the Mark's power, saying he should never have fought it. Dean and Cain fight it out with Dean losing as Cain still possesses some of his power even in the devil's trap and also because Dean refuses to give in to the Mark and draw on its power to win the fight. Ultimately, Dean gains the upper hand and kills Cain after Cain tells him he will never stop killing. Sam claims that if Dean could kill Cain himself without falling under the Mark's influence there is hope for him, but privately tells Castiel that Dean is in trouble.
10.17 Inside Man
In order to find out how to remove the Mark, Sam and Castiel break Metatron out of prison with help from Bobby Singer. After Castiel removes Metatron's grace, rendering him human, Metatron admits that he knows of no cure, saying that the Mark is God-level power and not even the Tablets have information on it though Lucifer may know.
At the same time, Dean is affected badly by the Mark, having nightmares about the carnage he's caused under its influence. When Rowena tries to kill him with three men under her control, Dean beats them but resists the Mark's attempts to make him kill them. Rowena tries to kill him with a spell, but the Mark renders him immune. Rowena later tells Crowley that the Mark is just a curse, but that she doesn't know how to remove it either.
Mark of Cain in Lore
In the Abrahmic religions it is said that after killing Abel, God cursed Cain, saying that he would be forever separated from his family and become a nomad. The mark of Cain was said to be placed on Cain by God so "Therefore whoever kills Cain, vengeance will be taken on him sevenfold, and the Lord appointed a sign for Cain, so that no one finding him would slay him." (Genesis 4-14)
