Grillo, a 64-year-old extravagant showman, has reinvented himself as a popular activist, prolific blogger and a hot favorite among the younger segment of Italy's angry electorate, which wants sweeping change in politics, economy and society.
About 47 million of Italy's 60 million citizens can vote and media reports suggest that many of them will turn out to elect 630 members of the lower house and 315 senators.
A substantial vote for Grillo will upset projections made before the comedian's Five Star Movement began to rise in approval ratings.
Center-left candidate Pier Luigi Bersani, 61, of the Democratic Party leads the polls while former conservative Prime Minister Silvio Berlusconi, 76, is regarded at the bottom of the list despite vigorous campaigning.
Grillo's activism is being compared by banks and the media with the Greek left-wing mavericks of the SYRIZA movement, which came a close second in last year's election in that debt-ridden eastern European country.
The European Union has indicated it may live with closet Communist Bersani if he forms a coalition with current centrist Prime Minister Mario Monti, 69. Whether the European Union can live with a coalition that also brings Grillo into the equation remains unclear.
Unlike SYRIZA in Greece, Grillo has little time for either the European Union or the euro and wants a referendum and the common currency ditched -- calls that won him huge crowds and cheers at election rallies.
Pollsters' findings suggest that Grillo may capture up to 20 percent of the vote, which would transform him into a power broker with unpredictable consequences.
Berlusconi called Grillo a threat to democracy but Bersani warns that a coalition that brings the entertainer into the government will lead to a logjam similar to conditions in Greece last year.
Other candidates include leftist Nichi Vendola, 54, anti-immigrant Roberto Maroni, 57, and Antonio Ingroia, 53, a former prosecutor involved in Mafia cases and now campaigning for judicial and other reforms under the banner of his Civil Revolution movement.
None of the three are likely to garner significant number of seats to win a majority but the votes cast for Vendola and Ingroia may help Bersani.
Bersani says he will continue Monti's reforms and attempts at fiscal discipline despite indications the economy is verging toward deeper recession. He is closer to French President Francois Hollande than German Chancellor Angela Merkel in advocating more spending to rekindle growth.
Bersani's alliance with openly gay Vendola has caused some divisions in the electorate.
Voting will close at 2 p.m. Monday and exit polls are expected to be released shortly thereafter. Official results are likely to be known later Monday.