In the White Wolf's roleplaying World of Darkness, Caine is the father of all vampires, whose story is based on the biblical story of Caine. In the world of Vampire: The Masquerade Caine, after his exile to Nod was taken in by Lilith, Adam's first wife, and taught to be self_sufficient.

He then became arrogant and three times refused salvation and forgiveness offered by archangels speaking on behalf of God, saying that by his own grace, and not God's, he would receive salvation. The archangels cursed him three separate times for his pride, giving him the powers and weaknesses of a vampire. Specifically, he received fear of flame from the archangel Michael, vulnerability to sunlight from the archangel Raphael, and immortality, along with the inability for him or his children to sustain themselves on anything but blood, from the archangel Uriel.

When playing Vampire: The Masquerade, the rules for fighting Caine are simple. All the book states is: "You lose".