- While playing a role with Frank Sinatra on the made-for-TV movie Contract on Cherry Street (1977), Sinatra remarked to De Santis that he "should have played the Godfather". De Santis cherished this comment to the end of his days.
- Established himself on radio beginning in May 1940 with "Pepper Young's Family", and later including "Mr. District Attorney", "March of Time", "Gangbusters", and "Under Arrest". He was inducted into the Pacific Pioneer Broadcasters Diamond Circle on May 17, 1985. He also did numerous Italian-language broadcasts. De Santis became known as a skilled character actor who could work convincingly with many dialect characters and was a perennially suave heavy.
- De Santis was born in New York City to Italian immigrant parents. His father, Pasquale DeSantis, was a tailor and his mother, Maria Paoli, worked in a paper flower factory. Made his Broadcast debut in Italian-language radio in 1931. Made his Broadway debut in Cyrano de Bergerac (1932-33).
- Studied sculpture and drama at New York University, his first performances were in Italian. From 1936-40, he taught sculpture in New York. Some of his work was exhibited in galleries at the 1939-40 World's Fair. A bust of actor Walter Hampden as Cyrano de Bergerac is on display at the Hampden Memorial Library. De Santis also taught acting at the American National Theater and Academy workshop, and dialect at the American Theater Wing. Was an active member of the Players' Club in New York, and the Masquers' Club in Los Angeles.
- In 1949, de Santis married actress Margaret Draper, whom he had met while both were appearing on "Pepper Young's Family" (a radio show). They had one son, Christopher, before divorcing in 1956. He relocated to Southern California to pursue TV and film roles.
- De Santis had two sons: David (from his first marriage) and Christopher (from his second).
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