He was detained in a high-security jail in L’Aquila, central Italy, where he continued treatment for his cancer in his cell.
In August, Messina Denaro was moved to the inmates’ ward of the local hospital, where his condition had declined in recent days.
This weekend, media reports said he was in an “irreversible coma”. Medics had stopped feeding him and he had asked not to be resuscitated, they added.
His arrest may have brought some relief for his victims, but the mob boss always maintained his silence.
In interviews in custody since being arrested, Messina Denaro even denied he was a member of the Cosa Nostra.
Investigators searched for years
After Messina Denaro went on the run, there was intense speculation that he had gone abroad – and he likely did.
But in the end, he was found to have been staying near his hometown of Castelvetrano in western Sicily.
Preparations are already under way for his burial in the family tomb in the town, alongside his father, Don Ciccio, according to the Corriere della Sera newspaper.
Don Ciccio was also head of the local clan. He was said to have died of a heart attack while on the run, his body left in the countryside, dressed for the funeral.
Investigators had been combing the Sicilian countryside for Messina Denaro for years, searching for hideouts and wiretapping members of his family and his friends.
They were heard discussing the medical problems of an unnamed person who suffered from cancer, as well as eye problems – a person who detectives became sure was Messina Denaro.
They used a national health system database to search for male patients of the right age and medical history, and eventually closed in.