Gianni Nicchi, 28, allegedly the No. 2 leader in the Sicilian mob, was found in an apartment in Palermo, the Italian news agency ANSA reported. Nicchi had been in hiding for three years.
Gaetano Fidanzati, 74, was arrested in Milan, the BBC said.
Berlusconi announced the arrests in Rome.
"This is the best response to all the slander made by irresponsible people who, by doing this, are only slinging mud," he said.
This week, a mob informant, testifying at the appeal of a Berlusconi associate in Turin, said a Mafia boss told him in 1994 that Berlusconi had helped the Mafia. Marcello Dell'Utri, a senator with a long relationship with the prime minister, is appealing his conviction and seven-year prison sentence.