Grandma Moses' At the Bend in the River (1948) is among the top lots at Sotheby's sale of American Paintings, Drawings and Sculpture in New York on October 2.
Valued at $40,000-60,000, the work is typical of the artist's homespun style.
While Moses (1860-1961) had experimented with painting (along with embroidery and quilting) in her younger days, her painting career didn't begin until she was in her 70s.
She was discovered in 1938, when a collector saw several of her paintings in a local store and bought them on a whim. In 1939, her work was exhibited at the Museum of Modern Art and by the following year she was given her first solo show.
By the 1950s Grandma Moses was a household name around the world.
A painting titled Sugaring Off holds her auction record after it sold for $1.2m in 2006.
We have this striking signed photograph from Grandma Moses, which was taken outside her home in Hoosick Falls in 1951.
South Street Spring by Fairfield Porter (1907-1975) is another highlight, with an estimate of $30,000-50,000.
Porter's fauvist inspired work is popular among collectors, with some of his best known pieces achieving figures around the $400,000-500,000 range.
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