The unusual vessel has links to Lord Byron after it was dug up by a gardener in the grounds of Newstead Abbey, the poet's Nottinghamshire home.
It is claimed Lord Byron took a fancy to it and he sent it to be polished and mounted for use as a drinking vessel.
The skull drinking cup has a silver coloured metal rim inscribed "SKULL DRINKING CUP USED BY LORD BYRON AT NEWSTEAD ABBEY".
Charterhouse, in Sherborne, Dorset, is auctioning the skull drinking up as part of its two day sale taking place on October 19 and 20.
They are selling it on behalf of an unnamed client from Devon and have given it an estimate of between £500 and £1,000.
Richard Bromell, from Charterhouse Auctioneers, said: "As one of the greatest British poets, a peers, a politician and a leading figure in the Romantic Movement Lord Byron needs little introduction
"Anything with an association or connection to Lord Byron is of great interest to collectors, even if it is part of a human skull.
"Lord Byron died in 1824 aged 36 years old. The engraving to the skull cup appears to be of a later date, probably towards the end of the 19th century..
"Although I am not a leading expert in skulls, I think you have to take this at face value and either believe the inscription of not.
"For me, I think the legend on the cup does hold some water."