The 67-year-old British rocker is selling an abstract painting by German artist Gerhard Richter at Sotheby's next month which is expected to fetch $14-19 million.
The price itself may raise barely an eyebrow in auction house circles, where Richter has long been one of the world's most sought after living painters with an auction record of $21.8 million set in New York in May.
But even amid soaring prices for top contemporary art, Clapton has done exceptionally well - the canvas on offer is one of three the former Cream musician acquired at Sotheby's in 2001 for a total cost of $3.4 million.
The work, more than two meters square and called "Abstraktes Bild (809-4)", "ranks alongside the very highest tier of Richter Abstracts housed in museums internationally," said Sotheby's, which is selling it.
Clapton is no stranger to the auction room.
Only last year he sold more than 70 of his guitars at a charity auction in New York, raising $2.15 million for the Crossroads Centre drug and alcohol rehabilitation center founded by Clapton in Antigua.
Abstraktes Bild was one of four in the series created by Richter in the mid-1990s. Three were sold to Clapton 11 years ago and a fourth belongs to the joint collection of the Tate and the National Galleries of Scotland.
A year ago, Richter, who is now 80, called the art market "daft", "absurd" and "impossible to understand".
Nevertheless, values of rare works have risen sharply for much of the last five years, in spite of broader economic concerns, as collectors from emerging markets like the Middle East, Russia and China help drive prices higher.
(Reporting by Mike Collett-White, editing by Paul Casciato)