The film opens with the police investigating the murder of high school girl Tomie Kawakami (Miho Kanno). They learn that in the months following the crime, nine students and one teacher have either committed suicide or gone insane. The detective assigned to the case learns that three years prior another Tomie Kawakami was murdered in rural Gifu prefecture. Other slain Tomie Kawakami's are discovered stretching all the way back to the 1860s, right when Japan began to modernize. The detective tracks down one of Tomie's classmates called Tsukiko (Mami Nakamura), an art student who is being treated for amnesia. She has absolutely no memory of the three-month period around Tomie's death, and is starting to suspect the cause has a supernatural source. Meanwhile, Tsukiko's neighbor is rearing a peculiar baby-like creature. Over the span of a couple weeks, it grows into a beautiful teenaged girl with orange eyes responding to the name of Tomie Kawakami.