Marge Sherwood is the most important female character in the book, but Patricia Highsmith resists placing her in the conventional love interest role. In some ways, her relationship to both men is very similar. Neither Dickie Greenleaf nor Tom Ripley takes her very seriously because both men are so self-centered. Ironically, after Dickie's death, Tom must take her more seriously because she poses a threat through the possibility that she will uncover the truth.

Marge is a young American novice writer living in Italy. She is romantically interested in Dickie, but he is not remotely interested in anything serious. Because he does not mislead her about his intentions, the reader cannot assume that he is taking advantage of her. Marge seems overly dependent on his approval but still knows that their relationship is fragile. When Tom starts to occupy more of Dickie's time, she grows jealous.

To Tom, Marge is initially an obstacle to his spending more time with Dickie—and to gaining further access to his luxuries and money. Tom's dismissive attitude toward her, and his extreme attachment to Dickie, prompts Marge to accuse Tom of being gay, which helps set in motion the events and emotional reactions that lead to Dickie's murder. Later, Marge is suspicious, but Tom adopts a different tone, sufficiently allaying her fears so that he decides not to kill her too.