Anthony Hopkins plays Dr. Hannibal Lecter, who has been living quietly in Florence under a false name and working as an art scholar. TMDB credits him in the same role in The Silence of the Lambs (1991) and again in Red Dragon (2002), which makes Hannibal the middle of his three appearances as Lecter on film.
Julianne Moore plays Clarice M. Starling, the FBI agent whose career stalls after a drug raid goes badly wrong. The role is a recast, since TMDB bills Jodie Foster first as Clarice Starling in The Silence of the Lambs (1991), so Hannibal passes the part to a new lead, billed second behind Anthony Hopkins.
Gary Oldman plays Mason Verger, a rich and badly disfigured survivor of a Lecter attack who offers money to anyone who can find him. TMDB bills Oldman third, behind Anthony Hopkins and Julianne Moore, and neither he nor Mason Verger is listed in the TMDB credits of Red Dragon (2002).
Ray Liotta as Paul Krendler
Ray Liotta plays Paul Krendler, billed fourth behind Anthony Hopkins, Julianne Moore and Gary Oldman. The role is a recast, since TMDB credits Ron Vawter as Paul Krendler in The Silence of the Lambs (1991), which makes Liotta the second actor to play the character on film.
Giancarlo Giannini plays Insp. Renaldo Pazzi, the Italian police inspector who begins to suspect that an art scholar in Florence is really Lecter. TMDB bills him fifth, and Francesca Neri is credited as Allegra Pazzi, who shares his character's surname. Giannini is new to the series, with no listing in the TMDB credits of Manhunter, The Silence of the Lambs or Red Dragon.
Željko Ivanek as Dr. Cordell Doemling
Željko Ivanek plays Dr. Cordell Doemling and is billed sixth in the TMDB credits, directly behind Giancarlo Giannini. Doemling is new to the series on film, because neither Ivanek nor the character appears in the TMDB credits of The Silence of the Lambs or Red Dragon.
Frankie Faison plays Barney Matthews, the character credited simply as Barney in The Silence of the Lambs (1991). TMDB also lists him as Lt. Fisk in Manhunter (1986) and as Barney in Red Dragon (2002), so he is the only one of the top billed actors here who appears in all four of those films.
Francesca Neri as Allegra Pazzi
Francesca Neri plays Allegra Pazzi, billed eighth and sharing a surname with Insp. Renaldo Pazzi, the inspector played by Giancarlo Giannini. Both roles belong to the Italian chapter of the story, set in Florence, and TMDB lists neither Neri nor Allegra Pazzi in the credits of The Silence of the Lambs or Red Dragon, so the character joins the series with this film.
Hazelle Goodman as Evelda Drumgo
Hazelle Goodman plays Evelda Drumgo, billed ninth in the TMDB credits. Three actors are credited as Evelda Drumgo's Bodyguard, and nearby credits include DEA and BATF agents, which ties the role to the drug raid that stalls Starling's career in the film's setup. Drumgo does not appear in the TMDB credits of The Silence of the Lambs or Red Dragon.
David Andrews as FBI Agent Pearsall
David Andrews plays FBI Agent Pearsall, billed tenth and one of several bureau roles in the credits, which also list special agents, an assistant director and an FBI mail boy. Pearsall is a new character for the films, absent from the TMDB credits of The Silence of the Lambs and Red Dragon.
Francis Guinan as FBI Asst. Director Noonan
Francis Guinan plays FBI Asst. Director Noonan, billed eleventh and holding the most senior bureau title in the credits. TMDB lists neither Guinan nor the character in The Silence of the Lambs or Red Dragon, so Noonan joins the series with this film, as do most of the officials around Starling.
James Opher as DEA Agent John Eldridge
James Opher plays DEA Agent John Eldridge, billed twelfth. His agency title, along with Ted Koch's BATF Agent Bob Sneed, points to the joint operation behind the drug raid in the film's setup. Eldridge is new to the series, with no listing for the character in the TMDB credits of The Silence of the Lambs or Red Dragon.