The socialist EDEK party decided by majority vote to leave the three-party administration, formally placing it in opposition for another three years until presidential elections in 2013 and ending a two-year partnership fraught with problems over a difficult peace process.
"We cannot endorse damaging strategies [...] Leaving this government is the politically responsible and morally right thing to do," EDEK chairman Yiannakis Omirou told a party conference.
The departure does not mean early elections, since Cyprus has a presidential system of government with a strong executive.
It does, however, reinforce the isolation Christofias may be sensing in peace talks with Turkish Cypriots and Mehmet Ali Talat, the Turkish Cypriot leader. Christofias, a communist party leader, was elected with votes from his own party, EDEK and the centrist Democratic Party in February 2008.
There was no immediate comment from Christofias on Monday, though aides had earlier urged EDEK not to take any rash decisions on leaving the government.
"It doesn't weaken [his position] because EDEK have been de facto opposition anyway, now it has become formal," said Hubert Faustman, a political analyst.
"As far as negotiations are concerned he never had their support," Faustman told Reuters.
Greek and Turkish Cypriots are attempting to reunite Cyprus as a two-zone federation, ending a partition in place since a Turkish invasion into north Cyprus in 1974 after a brief Greek-inspired coup.
The division of the island impedes Turkey's admission to the European Union, where Greek Cypriots represent the island, and is a source of friction between Greece and Turkey, which are NATO allies.
Christofias has been trying to balance delicate peace negotiations with growing discontent from his partners at what they see as concessions, particularly the extensive power-sharing he has apparently agreed to with Turkish Cypriots in the event of a peace deal.
Some members of the centrist Democratic Party, still in the government, share the Socialists' opposition to Christofias's offer of a rotating presidency with Turkish Cypriots and complain he started talks without finding a common basis for discussions.
"When a minority, through use of force and blackmail, demands a role in the state of equal weight with the majority, then any constitution which reflects such an undermining of historical realities will have an expiry date," Omirou said.
Peace talks are further complicated by presidential elections in northern Cyprus this April, which Talat, perceived as a moderate, could lose.
Any deal the two sides reach must go to referendum.
EDEK's departure will cause a government reshuffle. The party had two representatives on the island's 11-member cabinet, holding the agriculture and transport portfolios.
(EurActiv with Reuters.)
