Norwegian businessman Petter Olsen, whose father was a friend and patron of "Scream" painter Edvard Munch, owns the work, which will go on the block in New York on May 2, headlining the Impressionist and Modern Art sales.
Sotheby's described "The Scream" as "one of the most instantly recognizable images in both art history and popular culture, perhaps second only to the 'Mona Lisa.'"
There are four versions of the painting, which features a man screaming and clutching his head against a wavy, brightly-colored landscape, but this is the only one in private hands.
The influence of the disturbing picture, described by Munch as recording a moment of paralyzing anxiety during a walk with friends in the hills above Oslo, has few parallels.
Andy Warhol and "The Simpsons" reference the painting and it has been treated in countless books, films and exhibitions.
On two occasions, other versions of the painting have been stolen from museums, although both were recovered. Copies have adorned everything from student dorms to tea mugs and the work is arguably one of the few known equally to art experts and the general public alike.
Dating from 1895, "The Scream" offered by Sotheby's was done in pastel and is the only one in which one of the two figures in the background turns to look outward. The work will be exhibited at Sotheby's in London on April 13 and in New York starting April 27 ahead of the sale.
Simon Shaw, head of Sotheby's Impressionist and Modern Art department in New York, called "The Scream" the "defining image of modernity."
"Instantly recognizable, this is one of very few images which transcends art history and reaches a global consciousness. 'The Scream' arguably embodies even greater power today than when it was conceived," he said in a statement.
Olsen said in a statement that he wants proceeds from the sale to go toward establishment of a new museum and hotel on his farm in Hvitsten, Norway.
Munch died in his native Norway in January 1944 at the age of 80. In a poem the artist inscribed on the frame of the version coming up for sale, Munch wrote of feeling "deathly tired" and while letting his friends walk on, "I remained behind/ shivering with Anxiety -- I felt the great Scream in Nature."
The two thefts only added to "The Scream's" intensely high profile. In 1994, at the start of the Winter Olympics in Lillehammer, Norway, thieves took the primary version from the National Gallery in Oslo. It was returned unharmed later that year.
A decade later, masked gunmen stole the 1910 version from the Munch Museum in Oslo, along with another of his works. Both were recovered two years later.