Roy Lichtenstein's The Ring (Engagement) is to headline Sotheby's May 12 contemporary art evening sale in New York.
Valued at around $50m, it could set a new record for the artist's work.
Consignor Stefan T Edlis said: "Having amazed me from the moment I saw it, I find The Ring as beautiful today as it was all those years ago.
"We have lived with this iconic painting for nearly 20 years and hope it brings as much pleasure to the new owner as it has to me and my family."
The painting dates to 1962 and is part of a series inspired by comic book art (which includes the iconic Whaam!). Ironically, Lichtenstein was divorcing his first wife at the time.
It was last sold for $2.2m at Sotheby's in 1997.
Alexander Rotter, co-head of Sotheby's worldwide contemporary art department, commented: "The Ring (Engagement) is classic Lichtenstein.
"Dating from the key period and drawing on the artist's most important theme of romance and love, the painting is one of the most significant Lichtenstein's to appear at auction.
"In addition, the esteemed provenance and exhibition history make this an essential work by the revolutionary Pop master."
The present record for Lichtenstein's work stands at $56.1m, set by Woman with a Flowered Hat at Christie's in 2013.
Please sign up to our free newsletter to receive exciting news about art and antiques auctions.