Christie's will offer "Femme accroupie (Jacqueline)" - Crouching Woman (Jacqueline) - at a Nov. 13 sale in New York.
Painted in October 1954, the portrait hung for years in Picasso's private collection and has rarely been seen in public.
Christie's global president, Jussi Pylkkanen, says it is "a museum-quality painting" of "one of Picasso's most elegant muses." Roque was married to the artist from 1961 until his death in 1973.
The painting is one three portraits Picasso painted of Roque in his studio in the south of France on Oct 8, 1954, all showing her crouched with arms around her knees. The boldly colored painting shows the influence of the colorful cutouts of Henri Matisse, who died later that year.
It is being sold from a private collection, and Christie's estimates it will fetch $20 million to $30 million.
The painting will be on public display at Christie's London showroom from Saturday until Tuesday.
Picasso was one of the most acclaimed, and prolific, artists of the 20th century. His 1955 work "Les femmes d'Alger" sold in 2015 for $179 million - a record for a painting at auction.
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