George Stubbs' Tygers at Play is valued at £4m-6m ($6.6m-10m) in a sale of Old Master Paintings at Sotheby's London.
The auction is due to take place on July 9, with the work set to prove the headline lot.
Stubbs (1724-1806) is regarded as one of the finest English painters of his generation, best known for his exemplary horse paintings, and was enormously successful in his own lifetime.
The piece offered in the sale is one of a number the artist produced that depicts exotic animals.
These are among his most celebrated works - Portrait of the Royal Tiger sold for for £3.2m ($5.4m) in 1995.
Sotheby's commented: "demand for the enduring appeal of Stubbs's exotic animal portraits remains as high as it was during the artist's lifetime…
"Rarely, if ever, do works of this quality, importance and rarity appear on the open market for auction.
"The emergence of this picture for sale presents an exciting, once in a generation opportunity to acquire one of the masterpieces of eighteenth century British painting."
Stubbs' auction record was set at £22.4m ($37.9m) in 2011, when a painting titled Gimcrack on Hampstead Heath (1765) sold at Christie's London.
Other lots in the sale include works by Hieronymus Bosch, Bartolomo Cavarozzi and Pieter Brughel the Younger.
We have a range of art and photography memorabilia available.
Follow the link to get our free newsletter delivered straight to your inbox.