Rome is set to elect its first female mayor in a run-off vote in municipal elections.
Virginia Raggi, from the anti-establishment Five Star Movement, is seen as the favourite against Roberto Giachetti of the centre-left Democratic Party (PD).
Her victory would be a blow to Italy's Prime Minister Matteo Renzi.
His PD party may also lose in Italy's financial capital, Milan, and faces tough battles in Turin and Bologna.
Ms Raggi, a 37-year-old lawyer, won 35% of the vote in the first round two weeks ago, against 24% for Mr Giachetti.
Correspondents say a victory in Rome would give anti-globalist Five Star a platform for parliamentary elections due in 2018.
When in Rome shake up the politics
The next mayor of Rome will find a city mired in debts of more than €13bn (£10bn; $15bn) - twice its annual budget.
Romans are frustrated by potholes, piles of rubbish and serious deficiencies in public transport and housing, the BBC's James Reynolds in reports from the Italian capital.
Founded by comedian Beppe Grillo in 2009, Five Star has been campaigning against the corruption that has plagued Italian politics for years.
PD's Ignazio Marino resigned as mayor of Rome in October over an expenses scandal. The city has been without a mayor since then.
A much bigger scandal, involving alleged Mafia influence in Rome city hall, has fuelled Five Star's rise.
It is looking to establish itself as the main opposition party in the 2018 general election.
Prime Minister Renzi has staked his political future on an October referendum in which he wants Italians to back far-reaching constitutional reforms.
The plan is to end Italy's tradition of "revolving-door" governments and inject stability after years of party infighting and legislative logjams.