Dr. Hannibal Lecter is a character in a series of suspense novels by Thomas Harris. Lecter was introduced in the 1981 thriller novel Red Dragon as a forensic psychiatrist and cannibalistic serial killer. The novel and its sequel, The Silence of the Lambs, feature Lecter as one of the primary antagonists after the two serial killers in both novels. In the third novel, Hannibal, Lecter becomes a protagonist.

Throughout the beginning of the second season, Graham, who is now institutionalized, attempts to convince his skeptical former colleagues that Lecter is the real killer and begins pulling strings from within his cell in order to expose him. Meanwhile, Lecter begins to manipulate evidence from the outside, exonerating himself after the FBI's initial investigations into Graham's claims. Eventually, Graham persuades his friend and colleague Beverly Katz (Hetienne Park), a forensic scientist, to investigate Lecter in exchange for help on a case. She breaks into Lecter's house, where she find evidence of his guilt; Lecter catches her, however, and kills her. Angry and vengeful, Graham convinces a deranged hospital orderly (Jonathan Tucker) to try to kill Lecter, but the attempt fails. Lecter retaliates by taking as his lover Alana Bloom (Caroline Dhavernas), a psychologist for whom Graham has romantic feelings. Lecter then exonerates Graham by planting forensic evidence of Graham's alleged victims at the scene of one of his own murders, resulting in Graham's release. He also frames his colleague Frederick Chilton (Raul Esparza) by planting a mutilated corpse in his house and "influencing" his surviving victim Miriam Lass (Anna Chlumsky), into believing that Chilton had abducted and tortured her.  Graham resumes therapy with Lecter as an attempt to entrap him. Lecter quickly becomes aware of the ruse, but finds the experience fascinating and allows it to continue in order to explore the connection he feels with Graham. In an attempt to push Graham into becoming a serial killer, Lecter sends his psychotic former patient Randall Tier (Mark O'Brien) to kill Graham, but Graham kills and mutilates Tier instead - just as Lecter hoped he would. Later, Graham attacks tabloid reporter Fredericka "Freddy" Lounds (Lara Jean Chorostecki), who is investigating him and Lecter. Graham shares a meal with Lecter of what is implied to be her flesh, but it is soon revealed that Lounds is still alive and conspiring with Graham and Crawford to draw Lecter into their trap.  Lecter and Graham acquire a common enemy in Mason Verger (Michael Pitt), a wealthy sadist whom they both despise for emotionally and sexually abusing his sister Margot (Katharine Isabelle). Verger has them both kidnapped and prepares to feed them to his prize pigs; however, Lecter escapes and takes Verger hostage in Graham's house. He gives Verger a hallucinogenic drug cocktail, and tells him to cut off pieces of his own face and feed them to Graham's dogs. With Graham's tacit approval, Lecter then breaks Verger's neck with his bare hands, paralyzing him.  In the second-season finale, Graham and Crawford move to arrest Lecter against the orders of the FBI. In the ensuing struggle, Lecter seriously wounds Graham and Crawford, while a very much alive Abigail Hobbs pushes Bloom out of a window. Lecter then cuts Abigail's throat in front of Graham and leaves them to die as he flees before the police arrive. He is shown in a post-credits scene aboard a flight to France with his psychiatrist, Bedelia Du Maurier (Gillian Anderson).

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