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When it comes to God, Pittsburgh hairdresser Frankie Paige (Patricia Arquette) is a firm non-believer. However, after receiving a gift of some rosary beads, Frankie begins suffering from stigmata - bleeding wounds on her hands correlating with those suffered by Christ on the cross. Father Andrew Kiernan (Gabriel Byrne) is sent to investigate by the Vatican, and although initially dismissive, gradually begins to realize that Frankie is carrying an important message for mankind. However, Kiernan's corrupt superior, Cardinal Houseman (Jonathan Pryce), wants Frankie's message stopped, and is prepared to resort to murder to achieve his aims.