This article presents a new contextualization and interpretation of Michelangelo's composition, Christ and the Samaritan Woman, which was made for Vittoria Colonna around 1542. Known only through copies, it is an unusual representation of the theme, which eschews commentary on the sexuality or arrogance of the woman and instead includes elements that point to the woman's role in leading others to Christ. By reconsidering Colonna's own statements on the Samaritan woman and parallels found in Bernardino Ochino's comments, I argue that the design reflects the way Colonna positioned herself as a person of incomplete understanding who could still be saved through a direct encounter with Christ's words. The theme had particular resonance around 1542 when Italian reformers like Colonna faced increasing scrutiny from the Church. Indeed Colonna's interest in the subject may be a response to Ochino's flight from Italy in the face of threats from the Church.