Sotheby's New York said the last known surviving example of the stamp, issued in 1856, will be auctioned Jun 17 for the third time in its history.
The auction house said the sale would be a world record for an auction for a stamp if it meets the expected high bid amount.
Sotheby's said the stamp will be displayed in London and Hong Kong during the spring -- the first time it will have been seen by the public since 1986, when it was exhibited at the Ameripex '86 International Stamp Show in Chicago.
"I have been with Sotheby's all my working life, but before I knew about the world's greatest works of art, before I knew about the Mona Lisa or Chartres Cathedral I knew about the British Guiana," said David Redden, director of special projects and worldwide chairman of Sotheby's Books Department. "For me, as a schoolboy stamp collector, it was a magical object, the very definition of rarity and value, unobtainable rarity and extraordinary value. That schoolboy of long ago would be bemused and astonished to think that he would one day, years later, be temporary guardian of such a world treasure."