The film will span decades and deal with the disappearance of union boss Jimmy Hoffa which De Niro's Frank was involved with.
The Irishman is set to arrive in select theaters on Nov. 1 before it launches on Netflix on Nov. 27. The film is based on the Charles Brandt book I Heard You Paint Houses.
De Niro, on The Tonight Show, explained to Fallon what the term "I paint houses" means.
"It's an expression of killing somebody," De Niro said before explaining how it also means to clean up the mess left over from the killing and dispose of the body.