Silvio Berlusconi loses Milan and Naples in local polls
The run-off polls are seen as a key test of Mr Berlusconi's popularity, as he faces multiple corruption trials and sex scandals.
Centre-left candidate Giuliano Pisapia won in Milan with about 55% of the vote over Mayor Letizia Moratti.
Milan, Mr Berlusconi's power base, has been run by conservatives for 18 years.
The city, Italy's financial capital, is Mr Berlusconi's birthplace and where he got his start in business and politics.
Some six million voters were eligible to cast their ballots in 90 towns and six provinces, but the results in Milan and Naples are seen as most important.
Ms Moratti got 45% of the vote in Milan.
In Naples, Luigi de Magistris of the Italy of Values party won 65% of the vote in a landslide victory over Mr Berlusconi's candidate, Gianni Lettieri.
Mr Lettieri had been seen as the favourite, but failed to win an outright majority in the first round of voting earlier in May.
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