The Nottingham-based auction house reportedly hopes to fetch between £50 and £150 for the lot, although another slice of the Duke and Duchess of Cambridge's wedding cake sold for £2,597 when it was bought by an American royal fan in November 2013.
The slice of famous confectionary is being sold on behalf of Adrian Richardson, who is a former employee of Crown Speciality Packaging in Mansfield, Nottinghamshire.
Adrian, 59, was one of a small group of employees at the company who were sent some of the royal wedding cake to thank them for their work on a specially commissioned presentation tin.
The workers were given the cake in one of the tins they helped to design, along with a personal thank you note from Prince Charles and the Duchess of Cornwall.
Nigel Kirk, director of Mellors and Kirk Auctioneers in Nottingham, said he is interested in seeing if bids come in from outside the UK.
"Our royal family is greatly loved in many countries so it will be interesting to see where the bids come from," he said. "The cake itself is wrapped in greaseproof paper in the tin. It still smells quite wholesome but I wouldn't recommend that the buyer eats it - we wouldn't want them to get food poisoning.
"It will no doubt be popular with collectors of royal memorabilia."
Several edible mementos from royal weddings have been sold over the years.
In 2011, when yet another piece of cake from the Duke and Duchess of Cambridge's fruit cake went on sale, three other segments of royal wedding cake were also sold in the same auction.
One from the 1981 marriage of Prince Charles and Lady Diana Spencer, another from Prince Andrew and Sarah Ferguson's wedding in 1986 and a slice of the original cake from the Princess Anne and Captain Mark Phillips' big day.