In theater, he was considered one of the country's finest interpreters of Bertolt Brecht's plays in The Threepenny Opera and St Joan of the Stockyards.

[1] He is known to Italian horror movie buffs mainly for his three 1972 thrillers Twitch of the Death Nerve, Iguana with the Tongue of Fire and Your Vice is a Locked Room and Only I Have the Key.

He appeared in many Spaghetti Westerns such as The Good, the Bad and the Ugly (1966) (as the priest Pablo Ramírez, brother of Eli Wallach's character Tuco)[2] and in For a Few Dollars More (1965) as the cunning second-in-command Groggy (his first credited film role).

Pistilli committed suicide in his home in Milan just before he was scheduled to appear in the final performance of Terence Rattigan's Tosca on 21 April 1996.

However, according to his suicide note, Pistilli had suffered deep despair after making bitter public comments regarding the recent end of a four-year off-stage relationship with singer/actress Milva.