A bomb blast killed at least 25 worshippers during Sunday mass inside a Cairo chapel attached to the seat of the Coptic pope who heads Egypt's Christian minority, state media said.
Most of those killed were women. The dead included at least six children, Reuters reported.
The explosion ripped through the church at around 10:00 am (0800 GMT), Egyptian security officials said.
It was the deadliest attack on the country's Christian minority in recent memory.
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The blast in the church adjacent to Saint Mark's Coptic Cathedral in the Abbasiya neighbourhood shattered its glass windows and left a scene of carnage in the main prayer hall.
"As soon as the priest called us to prepare for prayer, the explosion happened," Emad Shoukry, who was inside the cathedral when the blast took place, told Reuters.
"The explosion shook the place... The dust covered the hall and I was looking for the door, although I couldn't see anything... I managed to leave in the middle of screams and there were a lot of people thrown on the ground," he said.
State television quoted a security official as saying a bomb made of TNT appeared to be used.
"Tell the sheikh, tell the priest, Egyptians' blood is not cheap," a crowd outside the church chanted, as ambulances lined up to evacuate the injured and ferry away the dead.
The church "is deeply loved by many Coptic faithful in Cairo and it has a regular parish presence," said Bishop Angaelos, the General Bishop for the Coptic Church in Britain.
He said services were being held in the adjacent chapel while St Mark's Cathedral was being renovated.
Nobody has claimed responsibility for the attack, but in the past terrorists in Egypt have targeted Christians, and Muslims they accuse of working with the government.
A bombing in Cairo on Friday on a road to the Giza pyramids killed six police and wounded three others in the deadliest attack on security forces in Egypt's capital in more than six months.