Orson Welles' Oscar for the 1941 film Citizen Kane is expected to fetch up to $1.2m (£586,000) when it goes under the hammer later.
The award, for best original screenplay, will be auctioned together with Welles' personal working copy of the script at Sotheby's in New York.
The 156-page script is expected to bring in another $120,000 (£59,000).
Many critics regard Citizen Kane, about a power-hungry newspaper baron, as one of the best films ever made.
The Oscar was believed to have been lost until it appeared at a 1994 Sotheby's auction.
A Los Angeles cinematographer had held it in secret, after being given it by Welles as payment for working with him.
After a lengthy legal battle, the award was returned to the Welles estate.
It was acquired by the Dax Foundation in 2003, a Los Angeles-based charitable foundation which is now selling the Oscar.
All of the proceeds will help fund the organisation's worldwide humanitarian efforts, a spokeswoman said.
Leila Dunbar, senior vice president at Sotheby's, said the prestige of the film added to the statuette's value.
"The movie had a star-studded cast," she said.
"Welles was fearless in the filmmaking and he had complete autonomy, all of which helped him create a landmark movie."
"The Citizen Kane script is the most important screenplay of all time," she added.