[2] Picerni joined the United States Army Air Forces during World War II[1] and served as a B-24 Liberator bombardier in the China-Burma-India Theater.

[3] As a young actor returning from the war, Picerni appeared in military pictures: in Twelve O'Clock High (1949) as a bombardier and as Private Edward P. Rojeck in Breakthrough.

This led to a Warner Brothers contract and a succession of roles at that studio including a Portuguese Socialist "Red" agitator in 1952's The Miracle of Our Lady of Fatima and the hero of the 1953 horror classic House of Wax.

[4] After Italian organizations began to complain about the use of Italian gangsters on ABC's, The Untouchables,[5] starring Robert Stack as G-man Eliot Ness, Picerni joined the cast in 1960 as Ness's number-one aide, Lee Hobson, a role that he played for the duration of the series.

)[6]: 1132  He also portrayed Ed Miller on O'Hara, U.S. Treasury (1971-1972)[6] and was featured as Dan Garrett on The Young Marrieds (1964–66)[6]: 1207 In 1954, Picerni was cast as the outlaw Rube Burrow in the syndicated western television series Stories of the Century, starring and narrated by Jim Davis.

[7] Picerni appeared in two episodes, "Gun Hand" and "Badge to Kill" of the syndicated western series 26 Men (1957–59).

[7] Between 1957 and 1960, Picerni was cast three times in different roles, the last as Duke Blaine, on the ABC/Warner Brothers western series, Colt .45, starring Wayde Preston.