Interior Minister Giuseppe Pisanu on Tuesday hailed the blitz as "an authentic blow to the Camorra", whose feuds have led to the killing of 23 people over the last month.
Some 1000 police officers stormed neighbourhoods worst hit by mafia violence, including Secondigliano and Scampia. By Tuesday, they had detained at least 51 of the 65 people marked for detention.
Police sources said clan boss Paolo Di Lauro's son was among those seized. If confirmed, it would mean a key player had been removed from the feud over the clan's territory.
"It's not the first operation and it won't be the last," Pisanu said. "They must continue with the same intensity until this wave of criminal violence is brought to an end."
Naples has been in the headlines for more than a month amid Wild West-like shootouts and the discovery of charred corpses in cars as rival mobsters fight for control of lucrative extortion and drug trafficking rings.
Naples is no stranger to crime and has one of the highest unemployment rates in Europe, but the latest wave of violence has shocked even long-time residents.
A group of Neapolitans protested against the mob war on Tuesday by lying down in one of the main squares and covering themselves with red-stained sheets - copying how many recent victims were found.
"We want to say to the Camorra, 'stop for the love of God'," said one of the groups organising the protest. "Human life isn't a commodity."