Messina Denaro was reportedly detained in a private clinic in Sicily’s capital Palermo. He is alleged to be a boss of Sicily’s notorious Cosa Nostra mafia.
Italian media reported that he had been receiving treatment when he was arrested just before 10:00 (09:00 GMT) and taken away by the Carabinieri.
He was tried and sentenced to life in jail in absentia over numerous murders.
These include the 1992 killing of anti-mafia prosecutors Giovanni Falcone and Paolo Borsellino, the deadly 1993 bomb attacks in Milan, Florence and Rome, and the kidnapping, torture and killing of the 11-year-old son of a mafioso turned state witness.
“This is a great victory for the state,” said Italy’s PM Giorgia Meloni.