The tomb reportedly contains the body of Lisa Gherardini, a silk merchant's wife who is believed to have sat for da Vinci’s famous painting. (Agencies)
Experts have been puzzled for centuries over the woman in the painting and the reason behind her cryptic smile.
In a bid to find the DNA they needed, scientists cut a round hole in the stone church floor above the family crypt of silk merchant Francesco del Giocondo.
Writer and researcher Silvano Vinceti plans to compare DNA from the bones with that of three women buried at the nearby convent of Saint Ursula.
Lisa Gherardini died in the convent as a nun in 1542. Experts hope some of the bones will belong to at least one of her blood relations, probably her son Piero.
"When we find a match between mother and child - then we will have found the Mona Lisa," said Vinceti.
He said that once a DNA match is made, an image of Gherardini's face can be generated from the skull and compared with the painting.
Da Vinci took about 15 years to complete the famous painting.
One of his favourites, the artist carried it with him until he died in 1519. It was then acquired by King Francis I, who ruled France from 1515 to 1547.
The painting was put on permanent display in the Louvre in Paris at the end of the 18th century. It was stolen in 1911 but was recovered two years later.
The tomb reportedly contains the body of Lisa Gherardini, a silk merchant's wife who is believed to have sat for da Vinci’s famous painting.