Berlusconi is under investigation on suspicion he had sex with a 17-year-old Moroccan girl and used his office to cover it up. He denies wrongdoing.
Prosecutors have focused on Berlusconi's villa in Arcore, just outside Milan, where he reportedly throws wild parties with young women.
Hundreds gathered in Arcore to demand the premier's resignation. Some wore masks of Berlusconi's grinning face covered by underwear. One woman wore a prosecutor's black robe in a show of support for the judiciary, which Berlusconi has repeatedly attacked.
A small group of protesters who had broken away from the main demonstration and tried to reach Berlusconi's villa scuffled with police, according to the ANSA news agency. The protesters hurled bottles and other objects at a police line blocking them, and police wielding batons charged at them, ANSA said.
The reports said a handful of people, both among the protesters and police, had been injured and two protesters detained.
It was the second anti-Berlusconi demonstration in as many days. On Saturday, thousands attended a rally in a Milan sports stadium, including notable left-leaning intellectuals such as Umberto Eco and anti-mafia author Roberto Saviano.
Berlusconi insisted in a message to his supporters Sunday that he will push ahead, saying there are no alternatives to his government. Berlusconi was elected in 2008 on a five-year-term.