The lyrics use biblical images to explain the relationship between a father and son. Cain was Adam and Eve's rebellious son who couldn't measure up to the goodness of his brother Abel. In the book of Genesis, Cain becomes jealous when God prefers Abel's offering to his own. He lures him out into a field and murders him, but he can't hide the act from God, who puts a mark of damnation on his forehead and sentences him to life as a restless wanderer. He can't even hope to be killed, for whoever sees the mark will know they "will suffer vengeance seven times over" if they were to kill him.
Springsteen's song examines Adam's role in raising a son that went down such a crooked path.
Springsteen calls this song "emotionally autobiographical." The bitter, but loving relationship between the father and son is similar to Springsteen's with his dad. Said Springsteen: "Our actual relationship was probably more complicated than how I presented it. Those songs were ways that I spoke to my father at the time, because he didn't speak and we didn't talk very much."
This was used in the movie Baby It's You, directed by John Sayles, who would direct Springsteen's videos for "I'm On Fire" and "Born In The U.S.A."
In the 2010 documentary The Promise: The Making of Darkness on the Edge of Town, sound mixer Chuck Plotkin described Springsteen's instructions for how the jarring assault of this song should sound next to the more melodic tunes on Darkness. Springsteen told Plotkin to think of a movie showing two lovers having a picnic, when the scene suddenly cuts to a dead body. This song, the singer explained, is that body.