In the Empty Chair Rhyme, a quadriplegic is desperate to improve his condition so he goes to the University of North Carolina Medical Center for a high-risk experimental surgery.

However in a twenty-four-hour period, a local teen is murdered and two young women are abducted. The prime suspect is a strange teenaged truant known as the Insect Boy, so nicknamed for his disturbing obsession with bugs.

Rhyme and his protégé Amelia Sachs are perfect for the case but suddenly Sachs begins to disagree, revealing her actual feelings. So ensues Rhyme's greatest challenge­ facing the criminalist whom he has taught everything he knows in a battle of wits, forensics, and intuition.