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- Anthony Hopkins as Dr. Hannibal Lecter
- Julianne Moore as Clarice Starling
- Gary Oldman as Mason Verger
- Ray Liotta as Paul Krendler
- Frankie Faison as Barney Matthews
- Giancarlo Giannini as Rinaldo Pazzi
- Francesca Neri as Allegra Pazzi
- Zeljko Ivanek as Dr. Cordell Doemling
- Hazelle Goodman as Evelda Drumgo
- Robert Rietti as Sogliato
- David Andrews as FBI Agent Pearsall
- Francis Guinan as FBI Asst. Director Noonan
- James Opher as John Eldridge
- Enrico Lo Verso as Gnocco
- Ivano Marescotti as Carlo Deogracias
- Danielle de Niese as Beatrice