Ernesto (Sergio Castellitto of Va Savoir) is a successful artist and devout atheist who finds out that his mother, whom he despised, is being considered for sainthood. Ernesto's young son, Leonardo (Alberto Mondini), influenced by his religion teacher, has developed a fear of God, whom he tries to shoo away like a pest. "If He's everywhere," Leonardo reasons, "then I'm not free -- even for a second." Ernesto's estranged wife, Irene (Jacqueline Lustig), encourages Leonardo's faith, and seems to be on the side of Ernesto's family, who are greedily clamoring to get Ernesto to participate in the canonization process. His mentally unstable brother, Edigio (Donato Placido), who will speak only to Ernesto, murdered their mother years earlier, and holds the key to her beatification. At a party, Ernesto insults a deranged monarchist, Conte Bulla (Toni Bertorelli), who then challenges him to a duel. Ernesto goes to complain to Leonardo's religion teacher, expecting to find an ugly old woman, and instead finds Diana (Chiara Conti), an impossibly beautiful young woman who admires his work. Ernesto meets the Cardinal (Maurizio Donadoni), and tells the man that his mother was "stupid" and "had no passion." "Loving someone is the best way to declare my atheism," he declares. But as he gets caught up in all the intrigue, Ernesto recognizes a connection to his hated mother that he cannot escape; he has the same mocking smile.

Marco Bellocchio's My Mother's Smile was shown at the 2002 New York Film Festival and at the 2002 Cannes Film Festival, where it won a Special Mention for the Prize of the Ecumenical Jury.