The BAU profiles an UnSub who surgically amputates legs, his slipshod methods often leading to the death of his test subjects. When a legless body is recovered in the desert and a second unwilling amputee shows up in the hospital, the team is stymied by the fact that the UnSub seems to have an excellent knowledge of anatomy but a poor understanding of surgical procedures or medical safety. As the UnSub begins to escalate things by transplanting legs from one victim to another, the team realizes that they're dealing with a highly dangerous killer with a God complex who believes that he is searching for the cure to an impossible medical problem.

Meanwhile, Reid becomes romantically attached to a brilliant scientist whom he only speaks to over the phone. But is she harboring a dark secret?