Dr. Kenzo Tenma is a young Japanese brain surgeon, working at Eisler Memorial Hospital in Düsseldorf, West Germany. Tenma is dissatisfied with the political bias of the hospital in treating patients, and seizes the chance to change things after a massacre brings fraternal twins Johan and Anna Liebert into the hospital. Johan has a gunshot wound to his head, and Anna mutters about killing; Tenma operates on Johan instead of the mayor, who arrived later. Johan is saved, but Mayor Roedecker dies; Tenma loses his social standing. Director Heinemann and the other doctors in Tenma's way are mysteriously murdered, and both children disappear from the hospital. The police suspect Tenma, but they have no evidence and can only question him.

Nine years later, Tenma is Chief of Surgery at Eisler Memorial. After saving a criminal named Adolf Junkers, Junkers mutters about a "monster." Tenma returns with a clock for Junkers, he finds the guard in front of Junkers' room dead and Junkers gone. Following the trail to the construction site of a half-finished building near the hospital, Tenma finds Junkers held at gunpoint. Junkers warns him against coming closer and pleads with him to run away. Tenma refuses, and the man holding the gun is revealed to be Johan Liebert. Despite Tenma's attempts to reason with him, Johan shoots Junkers. Telling Tenma he could never kill the man who saved his life, he walks off into the night, with Tenma too shocked to stop him.

Tenma is suspected by the police, particularly BKA Inspector Lunge, and he tries to find more information about Johan. He soon discovers that the boy's sister is living a happy life as an adopted daughter; the only traces of her terrible past are a few nightmares. Tenma finds Anna, who was subsequently named Nina by her foster parents, on her birthday; he keeps her from Johan, but is too late to stop him from murdering her foster parents. Tenma eventually learns the origins of this "monster": from the former East Germany's attempt to use a secret orphanage known as "511 Kinderheim" to create perfect soldiers through psychological reprogramming, to the author of children's books used in a eugenics experiment in the former Czechoslovakia. Tenma learns the scope of the atrocities committed by this "monster", and vows to fix the mistake he made by ending Johan's life.