The title comes from the biblical reference the mark of Cain where God declared that Cain, the firstborn son of Adam and Eve, was cursed with a black mark on his hand after killing his brother as a warning to others not to provoke the vengeance of God. Cain was given the mark by God as a sign of God's protection over Cain, a warning to others who might decide to kill Cain.
The major events in this episode occur or occurred in Colorado: 1. The fictional towns of Juniper Springs South (where Paladin finds the fugitive) 2. The fictional town of Bigley (where the back story occurred) 3. Denver -the original destination of Paladin (Richard Boone). Colorado was admitted to the Union on August 1, 1876. The time frame of this episode would be shortly before or shortly after Colorado became a state.