The film begins in the 1920's, in the Sicilian town of Bagheria (a.k.a. Baaria) where Giuseppe "Peppino" Torrenuova works as a shepherd to financially help his poor family. Over the next 50 years Giuseppe's life, as well as the life of the village, is observed. Giuseppe grows up, joins the Communist Party, marries a local girl (Mannina), has children and forges a political career for himself.

Young poetess Rose Elliot buys a book from a local antique dealer, a diary in Latin of an architect, E. Varelli. She learns of the Three Mothers, and believes her apartment building is one of their houses. She pleads her brother Mark, who is studying musicology in Rome, to come, because she is afraid. Mark's friend Sara reads her letter, which he left behind in class, and discovers the school is run by the Mater Lacrimarum, and is killed for this knowledge. The house of Mater Suspiriorum has already been destroyed, and by the time Mark arrives in New York City, he is investigating his sister's murder.

A psychic who can read minds picks up the thoughts of a murderer in the audience and soon becomes a victim. An English pianist gets involved in solving the murders, but finds many of his avenues of inquiry cut off by new murders, and he begins to wonder how the murderer can track his movements so closely.