Egyptian state television has reported that 25 people, mostly women, have been killed in an explosion near Cairo's Coptic cathedral.
Security sources said that six children were also among the dead and around 49 people were injured.
There was no immediate claim of responsibility.
The blast near Saint Mark's Coptic Orthodox Cathedral in the Abbasiya neighbourhood is the deadliest suspected attack on the country's beleaguered Christian minority in recent memory.
The cathedral is the seat of Coptic Pope Tawadros II.
A device containing about 12kg of the explosive TNT detonated on the women's side of the cathedral, security sources said.
Copts, who make up about 10% of Egypt's population of 90 million, have faced persecution and discrimination that spiked 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 throughout Egypt.
In 2011, a suicide bomber killed 21 worshippers outside a church in the coastal city of Alexandria.
Islamist extremists have regularly incited violence against Copts, especially since the military overthrow of Islamist president Mohammed Mursi in 2013.
They accused the Christians of supporting his ouster, which came after millions of protesters took to the streets demanding his resignation.
On 14 August 2013, mobs attacks dozens of churches across the country after police killed hundreds of pro-Mursi protesters in Cairo.