A New York Yankees cap worn by star first baseman Lou Gehrig (1903-1941) is among the lead lots in Heritage Auctions' Sports Collectibles Platinum Night Signature Auction in Cleveland.
The lot carries an estimate in excess of $200,000 ahead of the July 31 sale.
Gehrig is thought to have worn the hat during the legendary 1934 Triple Crown campaign, which would make this one of the most significant pieces of memorabilia associated with the star.
A 1952 Topps Mickey Mantle baseball card will likely prove another highlight, with an estimate of more than $200,000.
One of the legendary high number series produced by Topps, the card is among the most desirable in the history of the hobby.
The issue was printed in large numbers shortly before the close of the season, but went largely unreleased due to difficulties with distribution.
Most are thought to have been dumped at sea in order to clear space in the company's warehouse.
During the mid 1980s, collector and dealer Al "Mr Mint" Rosen received a phone call from a man offering to sell a collection featuring of 1952 high numbers.
The figure Rosen paid is unknown, although it was reportedly up in the six figures.
The rarest baseball card in existence is the T206 Honus Wagner, an example of which sold for $2.1m at Goldin Auctions back in April 2013.
The sale will also include the gloves Muhammad Ali wore in the 1971 Fight of the Century against Joe Frazier.
Check out all our sports memorabilia here.
Click here to get our free newsletter delivered straight to your inbox.