His mysterious death at the age of 38 has been blamed variously on malaria, an intestinal infection, lead poisoning from the oil paints he used or a violent brawl.
Now an intriguing new theory has been put forward for the demise of the rabble-rousing Renaissance artist Caravaggio – that he was killed in cold blood on the orders of the Knights of Malta to avenge an attack on one of their members.
The chivalric order, which was formed during the Crusades, hunted down the painter because he had seriously wounded a knight during a fight, according to Vincenzo Pacelli, an Italian historian and expert on Caravaggio.
The death of Caravaggio, who earned notoriety during his lifetime for his quick temper and hell-raising ways, has long been shrouded in mystery.
Some historians believe that he died of malaria in the Tuscan coastal town of Porto Ercole in 1610 and that he was buried there.
But Prof Pacelli, of the University of Naples, has unearthed documents from the Vatican Secret Archives and from archives in Rome which suggest that the artist was instead murdered by the Knights of Malta, who then threw his body in the sea at Palo, near Civitavecchia north of Rome.
If true, it was a violent end that Caravaggio himself foretold in one of his most famous works, David with the Head of Goliath (1610), in which he painted his own face onto the severed head of the slain giant.
The "state-sponsored assassination" was carried out with the secret approval of the Vatican, Prof Pacelli claims in a forthcoming book, Caravaggio – Between Art and Science.
"It was commissioned and organised by the Knights of Malta, with the tacit assent of the Roman Curia" – the governing body of the Holy See – because of the grave offence Caravaggio had caused by attacking a high-ranking knight, he said.
The decision to dump the body at sea explained why there are no funeral or burial records recording Caravaggio's death.
"Had he died at Porto Ercole, he would have been given a funeral, especially given the fact that his brother was a priest," Prof Pacelli said. "He would not just have been forgotten." Caravaggio, whose artistic genius was matched only by a supreme talent for creating enemies, was subjected to a violent attack in Naples in 1609 by unidentified assailants which left him disfigured.
Prof Pacelli believes they were almost certainly assassins sent by the Knights of Malta, an order which was founded in the 11th century.
The academic found historical documents which suggest that the Vatican, which objected to Caravaggio's questioning of Catholic doctrine, tried to cover up the truth of Caravaggio's death.
He discovered mysterious discrepancies in correspondence between Cardinal Scipione Borghese, a powerful Vatican secretary of state, and Deodato Gentile, a papal 'nuncio' or ambassador, in which the painter's place of death was cited as the island of Procida near Naples, "a place that Caravaggio had nothing to do with."
A document written by Caravaggio's doctor and first biographer, Giulio Mancini, claimed that the painter had died near Civitavecchia, but the place name was later scrubbed out and replaced by Porto Ercole.
Prof Pacelli has also found an account written 20 years after Caravaggio's death, in which an Italian archivist, Francesco Bolvito, wrote that the artist had been "assassinated".
Caravaggio – whose real name was Michelangelo Merisi – lived a turbulent life in which violent altercations forced him to flee from one city to another.
After finding fame in Rome for his distinctive "chiaro-scuro" painting technique – the contrast of shadow and light – he suddenly had to leave the city in 1606 after he was involved in a brawl in which he killed a man.
He eventually wound up in Malta, the headquarters of the Knights of Malta, where he was made a member of the order.
But by 1608 he was in prison, most probably after becoming involved in another fight, in which he wounded a knight.
He was expelled by the Knights on the grounds that he had become "a foul and rotten member" of the order and imprisoned in a castle dungeon.
He was released under mysterious circumstances and fled to first Sicily and then Naples.
He was heading to Rome in the hope of obtaining a papal pardon for the murder he had committed when he died.
Dr John T. Spike, a Caravaggio expert at the College of William and Mary in Williamsburg, Virginia, agreed that there was no evidence to prove the theory that Caravaggio died in Tuscany.
But he was sceptical of the idea that the tortured genius was murdered by the Knights of Malta.
"They had ample opportunities to kill him sooner – either when he was in Malta, or during the time he spent in nearby Sicily afterwards." Dr Spike believes the artist was killed – possibly accidentally – in a fight, and that his body was unceremoniously dumped.
In 2010, after a year-long investigation using DNA analysis and carbon dating, Italian researchers claimed to have found Caravaggio's bones in Porto Ercole.
They said they were 85 per cent sure that the remains belonged to the artists, but many historians have disputed those findings.