When a woman arrives home to her Manhattan apartment to find that her personal items have been rearranged while she slept, police initially dismiss her complaint. Nothing was stolen, and there's no sign of breaking and entering. But when the same woman turns up dead, Lincoln Rhyme and Amelia Sachs are brought in to investigate the murder. The soon learn that the murderer calls himself the Locksmith. He is obsessed with locks, slipping into homes in the dead of night and tying his victims up with knots or locks, ultimately strangling them.

Their hunt for the killer is interrupted when an internal investigation in the police force uncovers what seems to be a crucial mistake in one of Rhyme's previous cases. He is removed from the case, and must investigate the Locksmith in secret--with the help of Sachs and their new ally, Colter Shaw. The three work to untangle the mysteries behind the psychotic killer before he can set his ultimate trap.