The explosion took place at St Mark's Cathedral, main Coptic Christian cathedral, in Abbassyia district of central Cairo at around 10:00 am when the prayers were on, according to a statement by the Ministry of Health.
A bomb was lobbed into a chapel near the cathedral's outer wall, killing at least 25 people and injuring 31, Minister of Health Ahmed Emad said.
The reason of the large number of victims was because the blast took during Christian pray time and there were a large number of people inside the cathedral, a statement said.
Most of the victims are women and children, officials said.
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St Mark's Cathedral is the seat of Egypt's Orthodox Christian church and is home to the office of its spiritual leader, Pope Tawadros II.
The number of casualties may rise, the officials said, adding that the injured have been transferred to Dar El-Shefaa and Ain Shams University Hospital.
This is the third explosion in the country this week. On Friday, a blast killed six policemen and injured three others in Giza's Haram district and another occurred in Kafr El-Sheikh international road, killing one civilian and injuring three policemen.
Jihadists in Sinai often target Christians as well as Muslims they accuse of working with the government.
Copts, who make up about 10 per cent of Egypt's population of 90 million, have faced persecution and discrimination that increased during the 30-year rule of Hosni Mubarak, who was toppled by a popular uprising in 2011.
Dozens have been killed in recent years in sectarian attacks and clashes across Egypt.
In 2011, a suicide bomber killed 21 worshippers outside a church in the coastal city of Alexandria.
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