Picerni was born in New York City. He was an Eagle Scout in his youth and adolescence. After high school, Picerni studied drama at Loyola University.
Picerni joined the United States Army Air Forces during World War II and served as a B-24 Liberator bombardier in the China-Burma-India Theater. He flew twenty-five combat missions with the 493rd Bomb Squadron of the 7th Bomb Group and received the Distinguished Flying Cross. He was part of a mission that attacked and destroyed the actual bridge made famous in the film The Bridge on the River Kwai (1957). After the Japanese surrendered, Picerni became a Special Services officer in India. Following his discharge, he enrolled at Loyola Marymount University in Los Angeles, California.
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, the hero of the 1953 horror classic, House of Wax. After his departure from Warners, he appeared with Audie Murphy in Universal Studio's To Hell and Back.
When Italian organizations began to complain about the use of Italian gangsters on ABC's, The Untouchables, starring Robert Stack as G-man Eliot Ness, Picerni in 1960 joined the cast of the show as Ness's number-one aide, Lee Hobson, a role that he played for the duration of the series. (He was also seen in the program's pilot, playing Tom Lugari.):1132 He also portrayed Ed Miller on O'Hara, U.S. Treasury (1971-1972) and was featured as Dan Garrett on The Young Marrieds (1964-1966):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. That same year, he had a role in the pilot episode for the 1957-58 NBC detective series, Meet McGraw.
Picerni appeared in two episodes, "Gun Hand" and "Badge to Kill" of the 1957-1959 syndicated western series 26 Men, true stories of the Arizona Rangers, starring Tris Coffin. He appeared in the episode "Gypsy Boy" of the CBS Saturday morning series, Tales of the Texas Rangers. In 1957, he played a deserter in an episode of the syndicated Boots and Saddles.
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.
In 1958, Picerni played a milkman on the ABC sitcom, The Donna Reed Show. In 1959, He appeared in an episode of NBC's Northwest Passage adventure series about Major Robert Rogers's exploits during the French and Indian War. He also portrayed a police detective in the episode "The Quemoy Story" of Bruce Gordon's short-lived NBC docudrama about the Cold War, Behind Closed Doors.
Picerni made three guest appearances on Perry Mason during its nine-year run on CBS. In 1958 he played Charles Gallagher in "The Case of the One-Eyed Witness", and defendant Army Sgt. Joseph Dexter in "The Case of the Sardonic Sergeant". In 1963 he played murderer Walter Jefferies in "The Case of the Bouncing Boomerang." In 1964 he appeared in The Fugitive (TV series), in the episode "Search in a Windy City".
Picerni appeared in many other television series in guest roles, including Fury, The Rebel, Bourbon Street Beat, Here's Lucy, Gunsmoke, Hogans Heroes, Mannix, and The Red Hand Gang. In 1964, he portrayed Pierre Lafitte in, The Great Adventure.
For some 30 years, Picerni was the half-time master of ceremonies for the Los Angeles Rams home games.
Picerni married former ballet dancer Marie Mason, in 1947. They settled in Tarzana, California, to raise their family; they had eight children and ten grandchildren. Two of Picerni's children predeceased him.
His autobiography, Steps to Stardom: My Story, written with the help of Tom Weaver, was published by BearManor Media in 2007.
Picerni died from a heart attack on January 12, 2011 in Palmdale, California. Picerni is interred at the Roman Catholic San Fernando Mission Cemetery.