According to polls each of the candidates is to get roughly a third of the vote.
"It is very close, we are looking at a pollsters' nightmare," Pambos Papageorgiou, a research executive from the European University of Cyprus, said.
"In the end it will come down to party alliances and horse trading."
Nine candidates are standing and almost 516,000 people have the right to vote.
If no outright winner emerges, a second-round of voting will be held on Sunday with the top two candidates.
The contest is being billed as a choice between Papadopoulos's uncompromising stance on efforts to resolve the Mediterranean island's division and pledges by his main rivals to get peace talks back on track.
Cyprus has been split along ethnic lines since 1974 when Turkey invaded the northern part in response to an Athens-engineered coup aimed at uniting the island with Greece.
The winner of the election will be tasked with negotiating with the Turkish Cypriot community on a resumption of peace talks, stalled ever since Greek Cypriots rejected a United Nations settlement proposal in 2004.
Papadopoulos was a harsh critic of the blueprint.
His challengers say they will be more proactive about finding a settlement on the island, which has harmed Turkey's chances of joining the European Union.