The legendary musician famously came up with the melody for the song in his sleep, and he reportedly spent more than a year working on it with pianos and a guitar.
A 1907 Bechstein Concert Grand piano which was used in the process, and is now owned by Help! moviemaker Richard Lester, is expected to fetch $80,000 (£50,000) when it goes up for auction.
A spokesman for Omega Auctions in England says, "The piano is a fantastic piece of Beatles history. It's amazing to think that Yesterday, a song we all know and love, was written on it.
"It was undoubtedly been (sic) used by a number of other important stars of stage and film but most significantly it was used by Lennon and MCCartney during the filming of Help!"
The auction will take place in the Beatles' hometown of Liverpool, England on 20 March (14). Yesterday was released in August 1965 and was a number one hit in America.