Some thirty years ago, the centuries-old backing on the reverse of Michelangelo’s celebrated drawing of Cleopatra was removed, revealing a nearly complete sketch of a female head. This discovery prompted commentary by several scholars, who identified it as a variant version of, or preparatory study for, the image of Cleopatra on the recto. In this essay, I demonstrate that the uncovered image does not represent Cleopatra, but instead Medusa. The ensuing discussion pursues the question of meaning in the drawing, both intentional and residual. Asking why Michelangelo produced an image of the dangerous Gorgon, left it unfinished but did not entirely abandon it, leads to a consideration of the relationship between the legendary Medusa and the historical Cleopatra, and the basis on which Michelangelo might have identified with Medusa as a creative figure. The Medusa drawing is shown to be conceptually and expressively related to other Michelangelo work of the 1520s – the Medici Chapel sculptures and two groups of drawings, the grottesche and the teste divine – relationships from which a thematic preoccupation of the artist can be discerned.