After a train crash mangles the hands of concert pianist Stephen Orlac, a surgeon grafts on donor hands taken from a recently guillotined man; Orlac then discovers the donor was a convicted murderer and becomes convinced the hands retain a criminal will. His playing collapses, he feels compelled toward violence, and a murder in his family seems to confirm that the grafted hands act on their own.
The grafted hands are treated as if moral disposition and criminal intent live in the tissue itself, so that receiving a murderer's hands means receiving his murderousness. Agency is relocated from the person's mind to a transplanted organ, which is imagined to retain the memories and impulses of its original owner.
A sufferer's own belief that his hands are tainted produces the very symptoms (paralysis, dread, compulsion) that seem to prove the taint is real, so psychological suggestion is experienced as external invasion. The fear manufactures its own evidence, making an internal state indistinguishable from supernatural possession.
The apparent proof that cursed hands commit crimes is revealed to rest on a human deception: a living person, not dead tissue, staged the evidence and exploited the victim's belief. The book asserts that a seemingly occult horror can be fully accounted for by fraud plus the victim's own autosuggestion, without any transfer of will through flesh.