Mr. White and his team of government agents put the Jeffersonian Lab on lock down and demand that Brennan and her forensics team determine a cause of death for an unidentified, but highly classified set of remains. As the team gets to work, their findings lead them to suspect they are investigating one of the most famous presidential assassinations in history. Meanwhile, Booth's boss, Andrew Hacker, helps him break into the lab and determine the motive behind the mystery investigation, and a frustrated Cam worries that Michelle may be keeping a big secret from her.

Brennan teams up with a Canadian forensic podiatrist to determine the real victim after eight pairs of feet are found washed up on the U.S.-Canadian border, but seven pair belong to research. Elsewhere, Cam crosses a major boundary when she takes away Michelle's right to choose her own college.

A film adaptation of Brennan's latest book takes her and Booth to Los Angeles for the production, where Brennan criticizes the acting and disregard for science, but the trip takes a strange turn when a prop cadaver happens to be a real murder victim.