It's being billed as "one of the most extraordinary pieces of JFK-related memorabilia - and hence 20th Century Pop Culture - ever to surface" by Heritage Auction Galleries.
The item is question is the Presidential Seal cake side decoration from President John F Kennedy's May 29, 1962, birthday cake.
Today, the Madison Square Garden event is most remembered for Marilyn Monroe's seductive performance of "Happy Birthday, Mr President" as the giant cake was brought in to great fanfare.
The side decoration carries a pre-auction estimate of $5,000 or more and is being offered as part of Heritage's November Grand Format American & Political Memorabilia Auction.
Heritage's sale will present an important selection of John F Kennedy items assembled to mark the 50th anniversary of his 1960 election.
The Presidential Seal cake side decoration from President John F
Treasures going under the hammer include a gold presentation watch worn by JFK throughout the campaign, and what may well be the only example of Kennedy's trademark rocking chair to come with an authentication from the Kennedy family.
According to Heritage, the cake decoration has impeccable provenance and is being offered by the family of decorated New York Police Department Detective Patrick "Patty" Larkin.
Larkin worked security detail on the night of the event, took a shine to the piece, and was in the right place at the right time to get it out of Madison Square Garden and back to his home.
Apparently intended as a surprise gift for Larkin's girlfriend - today his widow - the cake decoration has resided in the family's collection for the last 48 years.
"I think that [Patty] was probably in and out of the kitchen a lot that night, as he probably escorted some of the stars in and out," said Mrs Larkin.
"It's no surprise that he became friendly with the help, that's the sort of man he was, and he was impressed with the cake decoration.
"At the end of the night he saw that it was going to be thrown out and he told a worker he really liked it, and wondered if he could have it.
"The worker said, 'that's between (you) and the garbage,' and the rest is now really history."
The piece, a potent relic of one of the most glamorous and iconic events in modern American presidential history, is likely to exceed its $5,000 estimate when it auctions on November 17.
Heritage Auction Galleries' headquarters in Dallas, Texas, will host the event.