The car will appear at the Kruse Collector Car Auction, Indiana, US on September 6, 2009 in one of the world's largest car collections.
Often called the Aero-Mobile for its unique custom plane-like design, Hughes' car will be the star among 5,000 collector vehicles.
It is expected to sell for a record price.
For the last few weeks, the 1936 Lincoln has been displayed at the Horsepower Museum in Auburn.
The car has already proven itself to be a brilliant investment. It first surfaced in 2004 during a museum owner's estate sale in a small town in Oregon and was purchased for just $10,000.
It has passed through a few owners' hands since then, each time selling for more and more money. The car was last sold in June, 2009 for over $1m in Tulsa, Oklahoma.
"This is one of the world's most unusual cars and I believe it's a great investment opportunity," said the car's current owner.
Hughes apparently considered the car to be an important part of his legacy, so he preserved it with his famously innovative plane 'The Spruce Goose' in a climate-controlled hanger in California.
The car is easily the most significant Hughes automobile, and is particularly special because Hughes completely redesigned it when his competitive and creative genius was at its peak.
He made it more dynamic, reduced the original weight by thousands of pounds, increased the length of the body and created a vehicle that could easily cruise at over 100 mph.
Some speculate that the very competitive Hughes intended to compete in a speed or endurance contest. He had already set the world's air speed record in a plane built under his direction.
But others say that he was developing his version of the ultimate concept car.
Seminal Hughes inventions also include retractable aircraft landing gear, the adjustable hospital bed and the modern day push-up bra to name only a few.