The European Union foreign policy chief Catherine Ashton said that remarks by Iranian President Mahmoud Ahmadinejad, who called Israel a "cancerous tumour with no place in a future Middle East,” were "outrageous and hateful".
According to reporters, Ashton's language was unusually forthright for the West's chief negotiator over Iran's nuclear program.
“The High Representative strongly condemns the outrageous and hateful remarks threatening Israel's existence by the Supreme Leader and the President of the Islamic Republic of Iran," Ashton’s spokesperson said a statement.
"Israel's right to exist must not be called into question,” he added.
Ashton called upon Iran “to play a constructive role in the region and expects its leaders to contribute to de-escalate tension and not fuel it.”
On Friday, Ahmadinejad told demonstrators in state-organized protests that "in the new Middle East, there will be no trace of the American presence and the Zionists".
As thousands of Iranians shouted "Death to America, death to Israel", the Iranian president called Israel a "cancerous tumour."
Earlier this week Iranian media reported that Iran's Supreme Leader Ayatollah Ali Khamenei had said Israel would one day be returned to the Palestinian nation and would cease to exist.
Ashton is acting as chief negotiator for six powers - the United States, Russia, China, France, Germany and Britain - that are trying to persuade Iran to scale back its nuclear program through economic sanctions and diplomacy.
They fear Iran's nuclear program aims at producing weapons.
Ashton and Iran's chief negotiator agreed at the start of August to hold more talks about Iran's nuclear work, but there has been no sign of imminent progress in the decade-long dispute.
On Friday, U.N. Secretary-General Ban Ki-moon also sharply criticized Ahmadinejad’s verbal attacks on Israel and called them "offensive and inflammatory.
"The Secretary-General is dismayed by the remarks threatening Israel's existence attributed over the last two days to the Supreme Leader and the President of the Islamic Republic of Iran," the UN press office said. "The Secretary-General condemns these offensive and inflammatory statements."
"(Ban) believes that all leaders in the region should use their voices at this time to lower, rather than to escalate, tensions," it said in a statement.
"In accordance with the United Nations Charter, all members must refrain from the threat or use of force against the territorial integrity or political independence of any state."