Gaiman's Cain is an aggressive, overbearing character. According to their appearance in Swamp Thing, the difference is that 'a mystery may be shared, but a secret must be forgotten if one tries to tell it'. They live as neighbors in two houses near a graveyard: Cain in the broad House of Mystery and Abel in the tall House of Secrets. This is based on the verse in the Bible which says that Cain was sent to live in the Land of Nod.

In Gaiman's Sandman universe, the biblical Cain and Abel live in the Dreaming at Dream's invitation. Jamie Delano also occasionally used them in a cameo role in his title Hellblazer. Gary Cohn and Dan Mishkin included them in the pages of Blue Devil in 1986. In 1985, the characters were revived by writer Alan Moore, who introduced them into his Swamp Thing series in issue #33, retelling the Swamp Thing's original origin story from a 1971 issue of House of Secrets. They were also both recurring characters in DC's Elvira's House of Mystery (1986–88). During the 1970s, they also co-hosted the horror/humor anthology Plop!. Originally they were the respective 'hosts' of the EC-style horror comic anthologies House of Mystery and House of Secrets, which ran from the 1950s through 1983-Cain debuting in House of Mystery #175 (1968) and Abel in DC Special #4 and House of Secrets #81 (both 1969). In issue #2, Lucien calls this unusual, and recent. In The Sandman, Cain is shown to kill Abel quite often. In the same issue, a contest-winning letter establishes that Cain and the House exist both in the dream world and the real world, and that only in the dream world does Cain continue to harm Abel. In Elvira's House of Mystery #11, Cain expresses shock at having killed his brother in recent times.

Although Cain would abuse Abel, he was not shown killing him until Swamp Thing vol. They were depicted together in Abel's first appearance, and parted to their respective Houses at the end of the story. Cain and Abel are based on the Biblical Cain and Abel, adapted by editor Joe Orlando with Bob Haney (writer) and Jack Sparling (artist) (Cain), and Mark Hannerfeld (writer) and Bill Draut (artist) (Abel).

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