Berlusconi, a flamboyant three-time former prime minister, cannot hold elected office because of a fraud conviction but has put forward European Parliament President Antonio Tajani as his prime ministerial nominee.
His four-party coalition was expected to win between 31 and 41 per cent of the vote, followed by the anti-establishment Five Star Movement with 29-32 per cent, according to an exit poll published by Rai public television.
The ruling centre-left Democratic Party was trailing in third place, according to the exit polls.
The vote comes after a gloomy campaign characterised by anti-immigration tub-thumping, widespread public anger at Italy's slow economic recovery and clashes between far-right and anti-fascist activists.
The killing of a teenaged recovering drug addict blamed on Nigerian immigrants last month inflamed tensions.
The murder prompted a racist "revenge" gun rampage by a fascist sympathiser, who shot and wounded six Africans.
The surge in right-wing and populist parties has drawn comparisons to Britain's vote to leave the European Union and the rise of US President Donald Trump.
Former White House adviser Steve Bannon -- the man who helped Trump ride a populist wave to power -- told the Italian press that a hookup between the anti-establishment Five Star Movement (M5S) and the anti-immigration League was "the ultimate dream".
"The Italian people have gone farther, in a shorter period of time, than the British did for Brexit and the Americans did for Trump," said Bannon, who was in Rome yesterday.
There was concern ahead of the vote that a lacklustre campaign and a confusing political landscape could push turnout down to a record low.
The interior ministry put nationwide turnout at 58.4 per cent at 1800 GMT four hours before polls were to close.
The national turnout in the last general election in 2013 was 75 per cent.
"We hope something will change because until now things have been very bad," said Enzo Gallo, an elderly shopper at a street market in Milan.
"The middle class no longer exists, the poor are becoming poorer, the rich are becoming richer and there is no social justice," he told AFP.
An alternative scenario of a deal between the anti-establishment Five Star Movement, which looks set to be Italy's biggest single party, and the far-right League led by Matteo Salvini has spooked European capitals.
Salvini, who is part of Berlusconi's coalition, has said he should receive the prime ministerial nomination if his party comes in front of Berlusconi's Forza Italia (Go Italy). Exit polls showed the two almost neck-and-neck.
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