Many major characters from Relic return:
- Police Captain Vincent D'Agosta - New York Police Department, initially in charge of the investigation.
- Dr. Margo Green - now assistant curator of the New York Museum of Natural History
- A. X. L. Pendergast - Special Agent for the FBI
- Bill Smithback - journalist, now crime reporter working for the New York Post
- Dr. Whitney C. Frock - Margo Green's former PhD mentor, evolutionary biologist, retired from the museum.
- Dr. Ian Dunbar - D'Agosta's FBI protector
New Characters:
- Sergeant Laura Hayward - New York police officer who worked on a unit to roust the homeless; a published author working on her Masters Degree in Sociology at New York University and an expert on the underground societies of New York. The second and third sections of the novel are preceded by excerpts from a paper she wrote that is awaiting publication. Later appears in the Preston&Child novels Brimstone , Dance of Death , The Book of the Dead and Fever Dream . In the years between Reliquary and Brimstone Hayward is promoted to captain.
- Captain Jack Waxie - D'Agosta's superior; takes over the investigation
- Anette Wisher - mother of murdered socialite Pamela Wisher, who then leads a crusade to save the city from crime.
- Redmond Horlocker - Chief of the New York Police Department
- Mephisto - the leader of an underground community beneath Central Park
- Dr. Simon Brambell - Chief Medical Examiner (his brother appears in other novels by Preston&Child)
- Bryce Harriman - crime reporter for the New York Times ; Smithback's rival
