The BAU travels to San Francisco when a series of murders leads the team to believe the possibility that the elusive "Zodiac Killer" might have returned. Meanwhile, Reid contemplates his own genius capabilities after he and Prentiss attend a seminar on violent crime hosted by the crime novelist Patricia Cornwell.
- Marissa Armijo - Marisa Devon
- Jimbo Barnett - Roger Smith
- Alexandra Choi - Reporter
- Claudia Choi - Agent Rebecca Lin
- Patricia Cornwell - Herself
- Michele Dawson - Tara Henson
- David Fraioli - Messenger
- Bill Frenzer - Hippie
- Joseph Fuhr - Dan Feinberg
- Christine Garver - Nicole Puli
- Danny Goldman - Bob Zablonsky
- Jonny Jay - David Atley
- Josh Latzer - Park Supervisor
- Frank Marshall - Alec Wyseck
- Jeff Newburg - Caleb Rossmore
- Toni Sawyer - Mrs. Zablonsky
- Brett Weinstock - Best Man
- Finn Wittrock - Harvey Morell
- David Parker Ray, The Toy Box Killer
- The Zodiac Killer
- Heriberto Seda, The New York Zodiac
- "Seito Sakakibara"
- "Feelin' Alright" by Joe Cocker
- "Lonely World" by Jeremy Silver
- Derek Morgan: "Three can keep a secret, if two of them are dead." — Benjamin Franklin
- Spencer Reid: "There is no greater sorrow than to recall in misery the time when we were happy." — Dante
- Marissa Armijo, the actress who portrays Marisa Devon, previously appeared on Criminal Minds, portraying Marissa in the Season Five episode Outfoxed.
- Christine Garver, the actress who portrays Nicole Puli, previously starred as Dawn Taggert in an episode of Suspect Behavior, the short-lived Criminal Minds spin-off.