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.
Raggi, a 37-year-old lawyer, won 35 percent of the vote in the first round two weeks ago, against 24 percent for Giachetti.
Correspondents say a victory in Rome would give anti-globalist Five Star a platform for parliamentary elections due in 2018.