The altar panels, painted by Italian monk Fra Angelico in 1438, disappeared after the altar was destroyed in the Napoleonic wars.
A former Bristol University art history expert found the panels in November hanging behind a door in the Oxford home of former academic, Jean Preston.
The rare works are to be auctioned in Dorset by Miss Preston's family.
Art mystery
Michael Liversidge, who made the discovery, said 77-year-old Miss Preston had been working as a curator of historic manuscripts at a museum in California when she bought the two paintings for about £200 in the 1960s.
Mr Liversidge said his friend had always enjoyed the panels which carry portraits of two saints.
Artist Fra Angelico became known as the angelic painter and specialised in monastery pieces.
He was beatified by Pope John Paul II - the first stage on the path to sainthood - in 1984.
The altar had housed eight panels, six had been found and the location of the remaining two had been seen as one of the art world's biggest mysteries.
Guy Schwinge, of auctioneers Duke's of Dorchester, said: "To put it in a nutshell we are dealing with two works of art painted by one of the greats, intended for his own church and commissioned by one of the greatest art patrons in history.
"It simply does not get much better than that."
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