The subject is from the New Testament (Mark 6). Salome had danced so well for King Herod that he swore he would grant her any request. Her mother, Herodias, who sought revenge on John the Baptist, persuaded Salome to ask for his head. The old woman behind Salome may be Herodias.

This is a late work by the artist, painted in the last three years of his life, perhaps in Naples where he resided from 1609 to 1610. No longer concerned with the incidentals of the narrative, Caravaggio focuses on the essential human tragedy of the story.