Italy's highest court has stated that a law giving the prime minister immunity from prosecution violates the constitution.
Silvio Berlusconi's approval ratings have already suffered after the summer's sex scandals.
Now, this decision could re-open outstanding corruption proceedings against Mr Berlusconi.
"The trials aren't going to be enough to force him to resign," said Franco Pavoncello, a professor of political science and president of Rome’s John Cabot University. “But his image is damaged and his allies may be tired of worrying about trials rather than running the country."
Berlusconi said the Constitutional Court that yesterday rejected his immunity was "politicized," and he attacked President Giorgio Napolitano as biased against his government. The ruling means that criminal trials against the premier for bribery, embezzlement and fraud will resume in coming months.
"It is an undeniable political right of Silvio Berlusconi, who was chosen by the electors, to govern and reform the country, but that cannot substitute his duty to respect the Constitutional Court and the head of state," Fini said in a statement, Bloomberg reports.
BBC News quoted Mr Berlusconi as sayiong, "I will defend myself... and show what stuff I'm made of."
The ruling means he could face trial in at least two court cases, including one accusing him of corruption.
But it does not mean Mr Berlusconi will be forced to resign, as long as he can keep together his conservative coalition, which dominates parliament, BBC News reports.