Marco Di Lauro, 38, was arrested at an apartment in Naples, where he lived with his wife, according to police.
Di Lauro, the fourth son of ex-Camorra boss Paolo Di Lauro, was sitting with his two cats and eating pasta when he was taken into custody in an operation that involved around 150 officers, Agence France-Presse reported.
"A great job and an extraordinary team operation," he said, calling the arrest "another blow to organized crime."
The 38-year-old was wanted over charges that include murder, drug trafficking, arson, armed robbery, racketeering and extortion, according to Europol.
The crime-fighting agency told Sky News that Di Lauro had joined a criminal organization that clashed with other mafia groups in 2000, starting the reported "secondigliano feud," which resulted in several killings.
Naples police chief Antonio De Lesu told reporters at a press conference that "unusual activity" had led police to the fugitive.
Di Lauro was considered the second most dangerous man in Italy, after Sicilian Mafia boss Matteo Messina Denaro, according to Italian media.
The 38-year-old had been on the run since 2004, with an international arrest warrant issued two years later. He was one of Italy's four most-wanted criminals, according to the country's interior ministry website.
In 2010, an informant said that Di Lauro was responsible for at least four murders, according to AFP.