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Renowned Parisian surgeon Doctor Gogol is obsessed with the beautiful horror theater actress Yvonne Orlac.  The doctor, who never misses a local guillotining, can always be found in the audience when Yvonne is on stage.  Following Yvonne's final performance, in which she plays a tortured victim, the actress receives flowers from her biggest fan, Gogol, who later comes to her dressing room to introduce himself.  When Gogol learns that Yvonne is planning to travel to England with her husband Stephen, a rising young pianist, he shows great distress at the news.

In another part of the city, Rollo, an American circus knife-thrower who killed his wife and knifed his father over the loss of a woman, is led to his guillotining.  Gogol attends the execution and, when he returns home he receives a call from Yvonne, who tells him that her husband has been injured in a tragic train wreck and is in need of the best surgeon in Paris.  Gogol, who is famous for his work in healing deformed children and mutilated soldiers, realizes while treating Stephen, that his hands are so badly damaged that they require amputation.  The doctor quickly decides to perform an experiment on the injured pianist by removing the hands of the executed Rollo and sewing them on to the amputee.

After procuring a medical release from the prefect, Gogol sends for the corpse and then successfully performs the operation.  Unaware of the experiment performed on him, Stephen returns to Yvonne, who is surprised to discover that her husband can no longer play the piano as he did before the accident.

When a bill collector pays the Orlacs a visit, Stephen becomes enraged with anger and, to everyone's amazement, hurls his penknife at him.  Later, Stephen again loses control of his hands when his stepfather, Henry Orlac, refuses to give him money.  Stephen throws a knife at him, but narrowly misses.

Meanwhile, Gogol takes advantage of Yvonne's gratitude for his services by asking her to perform a private show for him.  Stephen, troubled by his uncontrollable hands, seeks the opinion of Dr. Marbeau, who marvels at the recovery of hands that were once crushed seemingly beyond repair.  After some thought, the doctor concludes that Stephen's hands must not be his own.

Following Stephen's visit to Dr. Marbeau, newspaper headlines report that Stephen's stepfather has been found murdered.  Gogol, who killed Henry himself, convinces Stephen that he killed his own stepfather by disguising himself as the decapitated and revived Rollo and then telling him that the murder was committed with the hands that were removed from his body.  The frightened pianist is mesmerized by the disguised Gogol and finds proof that he killed his stepfather when he displays his mysterious knife-throwing skills.

Following Stephen's arrest, Yvonne decides to investigate the elusive Gogol herself, and goes to his home, where she finds a statue of herself in his parlor.  When Gogol returns home, he discovers Yvonne and begins to hear voices in his head telling him that "each man kills the thing he loves."  The mad doctor then grabs Yvonne and begins to strangle her with her hair.  Yvonne is rescued, however, when the police show up with her husband, who expertly throws a knife at the murderous Gogol and kills him.