Having just spent two months in Guatemala where she was identifying victims of genocide, renowned forensic anthropologist Dr. Temperance Brennan returns to Washington, D.C., where she is immediately detained by an agent from Homeland Security for carrying a human skull in her bag. Upon the arrival of FBI Special Agent Seeley Booth, Brennan is released, which she finds odd and realizes that it was his plot to get her to help him on an FBI case. She refuses to help until Booth promises her full participation in the case, which he reluctantly does.
At the crime scene, Brennan and Booth find human remains which were so thoroughly decomposed that only the bones remained. Brennan and her assistant, Zack Addy (Eric Millegan), determine the victim is a woman between 18 to 23 years old, and was a tennis player. Back at the Jeffersonian Institute, Brennan argues with her boss, Dr. Daniel Goodman, who feels no qualms about assigning her to work with other federal agencies without her permission.
Inside the Medico-Legal Lab of the Jeffersonian Institute, Brennan examines the victim's remains while her colleagues inquire about the resemblances between them and the characters in her new book, Bred in the Bone. Dr. Jack Hodgins (T. J. Thyne), an entomologist, tells Brennan that the victim has been in the pond for more than two summers. Hodgins has also found small bone fragments in the silt, which he guesses are rana temporaria or simply, frog bones. Angela Montenegro (Michaela Conlin), a forensic artist, uses a computer program she has developed, called the Angelator, to make a three dimensional holographic reconstruction of the skull, which Brennan reassembled. The identity of the victim is revealed to be Cleo Louise Eller, who was a missing senate intern and was rumored to have had an affair with Senator Bethlehem.
Brennan wants to confront the Senator but Booth argues that the Senator is not the only suspect. The Senator's aide, Ken Thompson, was Cleo's boyfriend. There is also Cleo's stalker, Oliver Laurier. Booth tells Brennan that they have a major case and that FBI Deputy Director Cullen is going to want to set up a special unit to investigate, which means they are going to have do things by the book and wants her to stay at her lab. Brennan blackmails Booth until he agrees to let her come with him into the field.
Based on the particulates embedded in Cleo's skull, Hodgins determines that Cleo's skull may have been smashed by a sledgehammer on a cement floor and diatomaceous earth. By the distinctive damage done to her finger pads and the way the body was hidden, the team determines that the murderer had put a lot of effort into hiding the victim. Hodgins also reveals that Cleo was taking medicine for her depression, while Brennan realizes that the small bones found with Cleo's body are not frog bones but fetal ear bones, indicating Cleo Eller was pregnant.
Hodgins, a conspiracy theorist, convinces Brennan that they may never find the truth as Senator Bethlehem may have enough power to impede the investigation. Without telling Booth, Brennan decides to confront the Senator. Consequently, Deputy Director Cullen removes Booth from the case but Brennan refuses to give up. With the help of her fellow scientists, she uncovers that Cleo Eller's boyfriend Ken Thompson, had killed Cleo because he feared the scandal Cleo's pregnancy would cause and affect his career.