French Embassy spokeswoman Bernadette Abou Bechara said a French woman, a tourist, was killed in the blast on Thursday.
The US citizen died overnight from wounds caused by the attack, Egypt's tourism minister said on Friday.
Ahmad al-Maghrabi said the man was one of four US citizens wounded in the blast. US embassy spokeswoman, Micaela Schweitzer-Bluhm, said several Americans were targeted in the explosion. She also confirmed that the dead American was a tourist.
An earlier Egyptian interior ministry statement had said four people were killed and the wounded - four French, three Americans, an Italian, a Turk and nine Egyptians - were taken to hospital.
Police sources said a man on a motorcycle threw the bomb into the busy tourist area in the centre of the Egyptian capital at approximately 5.45pm (1545 GMT), but the subsequent ministry statement made no mention of what caused the blast.
One witness said it appeared a man on a motorcycle set off a bomb in the middle of a group of foreigners.
Rabab Rifaat, an Egyptian woman who was shopping in a store several metres from the blast, said the explosion appeared to have been caused by a man who was either carrying a bomb or had it on his motorcycle.
She said she heard "a boom, a horrible sound, very loud. Everyone started running", and then she saw a decapitated head flying through the air.
Egyptian police cordoned off the
site of Thursday's deadly blast
She said she also saw six or seven bodies on the ground, some of them "foreign-looking", but it was unclear if they were dead or wounded.
A number of bazaars surround al-Azhar, one of the most prestigious Islamic institutions in the Sunni Muslim world, in Cairo's old city.
Egypt has largely been calm since it suppressed a fierce campaign of violence by armed Muslim groups seeking to overthrow the government in the 1990s.
The last major anti-government attacks came in late 1997. In September of that year, two armed men fired automatic rifles at a tour bus parked outside the Egyptian Museum in central Cairo, killing 10 people - mostly German tourists.
A blast last October in a Taba
resort killed 34 people
A month later, assailants killed 58 foreign tourists and four Egyptians in an attack at a pharaonic temple in Luxor, southern Egypt, the worst such attack ever.
And last October, violence against foreigners returned after explosions hit several hotels in the Sinai peninsula, including one in the resort of Taba, popular with neighbouring Israelis on short visits.
The blast killed 34 people and Egyptian authorities linked the attack to Israeli-Palestinian troubles.
It was not clear immediately though as to who could have been behind the latest blast and what could have been the motive behind it.
Ahmad Musa, deputy chief editor of al-Ahram newspaper, told Aljazeera it was unclear whether the explosion was a terrorist act.
"Nobody can confirm that the blast was a terrorist act targeting the tourists, as Egypt has never witnessed any hostile action against the tourists since 1997. What had occurred in Taba was directed to the Israelis in retaliation for their deeds in Palestine. Thus, we cannot link this incident to Taba operation".
"Therefore, the first possible suspect will be al-Qaida dormant or inactive cells , but they are very weak in Egypt"
Another Egyptian journalist from the same newspaper, Ahmad al-Massalamani, also pointed out that Islamic Jihad groups had not been involved in violence since 1997.
"Therefore, the first possible suspect will be al-Qaida dormant or inactive cells, but they are very weak in Egypt.
"The second possible suspect could be a new generation of Egyptian Islamic Jihad, who are unknown to the security forces or to the political analysts," he said.
State of emergency
Aljazeera correspondent Lina al-Ghadban said some people thought Thursday's blast might lead to an extension of the nation's state of emergency.
The area where the blast took place had recently undergone renovations. Shop owners expected it would attract more tourists, but now they worry the explosion will be a blow to tourism, al-Ghadban said.
A pro-reform demonstration near the al-Azhar mosque is to take place on Friday after noon prayers, al-Ghadban said, but it was not clear whether heightened security would force the event to be cancelled.