When the beautiful and mysterious Tomie Kawakami transfers into a new high school class, she immediately becomes a magnet for obsessive male attention and a target for intense female jealousy. Her arrival quickly destabilizes the entire classroom, turning petty infighting into a spiral of violence and madness. The boys in her class, including the teacher Satoru Takagi, fall under her spell, while most of the girls alienate and bully her. The only exception is the introverted and lonely Reiko Matsuhara, who is intrigued rather than hostile toward the new student, and the two form a close, intense friendship.

As Reiko gets closer to Tomie, she learns that her friend despises men and that those who fall in love with her inevitably try to harm her. In a series of disturbing events, Tomie takes brutal revenge on her bullies, nearly killing one and psychologically torturing her lackeys. When a group of boys, including Kenichi Yamamoto and his friend Inoue from the photo club, attack Tomie and Reiko one night, they manage to slice off one of Tomie's ears. But as Reiko watches in horror, the severed ear begins to grow small limbs and crawl away, revealing the true supernatural nature of her companion. Tomie's ear then completely regenerates, and she confesses her inhumanity to Reiko, promising to show her what hell is truly like before disappearing into the night.

The narrative is framed as a flashback years later, when Yamamoto and Reiko are the only two to attend a class reunion. While Reiko reflects on the traumatic events of her friendship with Tomie, Yamamoto confesses that he only came to find Tomie again. After discovering a piece of Tomie's living heart in Reiko's bag, he kills her to take it, but Reiko immediately regenerates, revealing that she was transformed into a Tomie clone long ago when a duplicate of the monster grew from the blood on her uniform. The film concludes as Takagi, the former teacher, returns and kills the new Tomie, vowing to destroy her permanently, setting the stage for the events of the original Tomie film.