The attack came two days after a bomb elsewhere in Cairo killed six policemen, an assault claimed by a shadowy group that authorities say is linked to the outlawed Muslim Brotherhood. Islamic militants have targeted Christians in the past, including a New Year's Day bombing at a church in Alexandria in 2011 that killed at least 21 people.
Egypt's official MENA news agency said an assailant lobbed a bomb into a chapel close to the outer wall of St Mark's Cathedral, seat of Egypt's Orthodox Christian church and home to the office of its spiritual leader, Pope Tawadros II. Egyptian state TV gave the casualty toll.
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Members of the special police forces stand guard to secure the area around St. Mark's Coptic Orthodox Cathedral after Sunday's explosion inside. (Mohamed Abd El Ghany/Reuters)
Witnesses said the explosion may have been caused by an explosive device planted inside the chapel. Conflicting accounts are common in the immediate aftermath of attacks.
The blast took place as a Sunday mass being held in the chapel was about to end and coincided with a national holiday in Egypt marking the birth of Islam's Prophet Muhammad. Most of the victims are thought to be women and children.
A device containing about 12 kilograms of the explosive TNT detonated on the women's side of the cathedral, security sources said.

An Associated Press reporter who arrived at the scene shortly after the blast saw blood-stained pews and shards of glass scattered across the chapel's floor. Men and women wailed and cried outside.
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An employee of the cathedral checks for damage from the blast. (Mohamed Abd El Ghany/Reuters)
"I found bodies, many of them women, lying on the pews. It was a horrible scene," said cathedral worker Attiya Mahrous, who rushed to the chapel after he heard the blast. His clothes and hands were stained with blood and his hair matted with dust.
"I saw a headless woman being carried away," Mariam Shenouda said as she pounded her chest in grief. "Everyone was in a state of shock," she said.
"There were children. What have they done to deserve this? I wish I had died with them instead of seeing these scenes," she added.
There was no immediate claim of responsibility for Sunday's attack.
Egypt has seen a wave of attacks by Islamic militants since the military overthrew President Mohammed Morsi, a freely elected leader who hailed from the Brotherhood, in 2013. Many of Morsi's supporters blamed Christians for supporting the overthrow, and scores of churches and other Christian-owned properties in southern Egypt were ransacked that year.
The authorities have since 2013 waged a sweeping crackdown, jailing thousands of mostly Islamist dissidents and killing hundreds in clashes sparked by demonstrations.