As counting got underway on Monday following the close of polling stations late on Sunday, the right's Nello Musumeci was projected to have 37.3 percent of the vote and the Five Star's Giancarlo Cancelleri 36.8 percent, the EMG polling institute calculated for La7 television.
The Piepoli institute, meanwhile, gave Musumeci 36 percent to Cancelleri's 34 percent, according to RAI television.
Final results are not expected until later on Monday, but the projections appear to confirm the expected loss for leftwing rivals, with the centre-left Democratic Party of former premier Matteo Renzi seen garnering 20 percent of the vote.
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The Sicily vote is being watched as a barometer of public sentiment ahead of general election expected next year.
A new electoral system, voted in last month, favours alliances. If the results are confirmed, it would prove the power of a coalition made up of Forza Italia (Go Italy) and its rightist allies, the anti-immigrant Northern League and the Brothers of Italy. While the bloc is considered unlikely to be able to win an absolute majority on the national stage, snapping up the most votes would put it in control of any coalition it formed with the left.
Berlusconi, the four-time former premier who was declared politically dead after a series of scandals and open heart surgery last year, hopes a Sicily victory will launch him back in the centre-right driving seat.
One of his loudest challengers, comedian and M5S founder Beppe Grillo, had told Sicilians "the choice is simple: us or them, the future or the past, hope or failure, citizens or traditional parties". As one of the poorest regions in Italy, Sicily has proven open to the anti-establishment M5S, which wooed many with a promise of establishing a basic universal income.
But it appeared voters may have been more convinced by Berlusconi's portrayal of himself as a pro-European moderate who represented the only real defence against populism. The League had seen Sicily as a testing ground for expanding its reach beyond Italy's northern regions.
A bitterly feuding left failed to get anywhere near the top, losing control of the island.
The only consolation for Renzi was that the MPD -- a new party formed this year after the PD's far-left flank broke away -- did less well than he feared, taking home between seven and 11 percent. The result could still spell bad news not just for the left nationally but also for the former PM, who wants his old job back.
"Renzi is preparing for the probable Sicilian nosedive like a man whose enemies are at the door and the supplies are running out," political commentator Tommaso Ciriaco said.
The 42-year old has been accused of causing a debilitating rift in the left that may not be easily fixed.
Voter dissatisfaction in Sicily -- where the rate of youth unemployment is nearly 60 percent -- translated into a pitiful turnout. While only 47 percent of eligible voters cast their ballots in the last regional election in 2012, a record low, figures at 7pm on Sunday suggested even fewer had done so this year.
"The polling stations open under a dark cloud, amid controversy over the risk of vote-rigging," La Repubblica daily said, referring to claims the decision to wait overnight before beginning the count increased the chances of fraud.
The interior ministry was tightening controls in the Mafia heartland in response, it said.
By Alessio Tricani with Ella Ide in Rome