Italian scientists are seeking to exhume the body of Leonardo da Vinci to conduct carbon and DNA testing.
If the skull is intact, the scientists can go to the heart of a question that has fascinated scholars and the public for centuries: the identity of the Mona Lisa.
One theory is that the female figure in the painting is in fact a disguised self-portrait of Leonardo.
Recreating a virtual and then physical reconstruction of Leonardo's face, they can compare it with the smiling face in the painting, experts involved in the project said.
"We don't know what we'll find if the tomb is opened, we could even just find grains and dust," said Giorgio Gruppioni, an anthropologist who is participating in the project.
"But if the remains are well kept, they are a biological archive that registers events in a person's life, and sometimes in their death."
The leader of the group, Silvano Vinceti, said he plans to press his case with French officials in charge of the purported burial site at Amboise Castle early next week.
But the Italian enthusiasm may be premature.
In France, exhumation requires a long legal procedure, and precedent suggests it's likely to take even longer when it involves a person of great note such as Leonardo.
Jean-Louis Sureau, director of the medieval-era castle located in France's Loire Valley, said once a formal request is made, a commission of experts would be set up. Any such request would then be discussed with the French Ministry of Culture, Mr Sureau said.
Leonardo moved to France at the invitation of King Francis I, who named him "first painter to the king."
He spent the last three years of his life there, and died in Cloux, near the monarch's summer retreat of Amboise, in 1519 at age 67.
The artist's original burial place, the palace church of Saint Florentine, was destroyed during the French Revolution and remains that are believed to be his were eventually reburied in the Saint-Hubert Chapel near the castle.
The tombstone says simply, Leonardo da Vinci; a notice at the site informs visitors they are the presumed remains of the artist, as do guidebooks.
"The Amboise tomb is a symbolic tomb; it's a big question mark," said Alessandro Vezzosi, the director of a museum dedicated to Leonardo in his Tuscan hometown of Vinci.
Arguably the world's most famous painting, the Mona Lisa hangs in the Louvre in Paris, where it drew some 8.5 million visitors last year.
Mystery surrounded the identity of the painting's subject for centuries, with speculation ranging from the wife of a Florentine merchant to Leonardo's own mother.
That Leonardo intended the Mona Lisa as a self-portrait in disguise is a possibility that has intrigued and divided scholars.