In a speech marking Eid al-Fitr, the end of the Muslim holy month of Ramadan, Ayatollah Ali Khamenei said "the big powers have dominated the destiny of the Islamic countries for years and installed the Zionist cancerous tumour in the heart of the Islamic world," according to the official IRNA news agency.
"Many of the Islamic world's problems come from the existence of the sham Zionist regime," he was quoted as saying.
The "tumour" characterisation was a repeat of terms Khamenei and President Mahmoud Ahmadinejad have long used to portray Israel as an illegitimate state in the Middle East that will inevitably disappear.
In the most recent incidents, last Wednesday Khamenei called Israel a "bogus and fake Zionist outgrowth" and Ahmadinejad on Friday said: "The Zionist regime and the Zionists are a cancerous tumour."
Those expressions were met with condemnation on Friday by the UN's Ban, the United States, EU foreign policy chief Catherine Ashton and France's foreign ministry.
Ban, whom Iran has invited to attend a summit in Tehran at the end of the month, was "dismayed" by the "offensive and inflammatory statements," according to his spokesman.
Ashton's office and a spokesman for the US National Security Council both slammed the remarks as "hateful", while a French foreign ministry spokesman said they were "outrageous and totally unacceptable."
In his speech on Sunday to top Iranian officials and Muslim ambassadors in Tehran, Khamenei said the issue of Israel and its control over the Palestinian people was the main problem for Islamic countries.
"All Islamic governments and people have to pay attention to the very dangerous plot (by the West) that seeks to obscure this issue by creating divisions within the Islamic nation," he was quoted as saying.
He accused the world's "big powers" of using "the old method of 'divide and conquer'" on Islamic states, but said the popular revolts shaking the Arab world were changing the situation.
Tensions between Israel and Iran are taut because of threats by the Jewish state to attack nuclear facilities in the Islamic republic to prevent it reaching the capability to produce nuclear weapons.
Israel and its ally, the United States, accuse Iran of seeking to develop an atomic arsenal.
Tehran denies that, and says its nuclear programme is exclusively peaceful. Its military chiefs warn they will destroy Israel if it attacks.
On Saturday, General Amir Ali Hajizadeh, the head of the aerospatial division of the Revolutionary Guards that is in charge of Iran's missiles, said: "Iran's response to any aggression will be rapid, firm, destructive and broad."