The explosion went off inside a Coptic Christian church in the city of Tanta north of Cairo as worshippers were celebrating Palm Sunday.
Egyptian state media reported 21 people had been killed and a further 38 wounded.
Footage from CBC TV from inside the Mar Girgis (St George's) Coptic Church showed dead bodies covered with papers.
Coptic Christians make up about 10 percent of Egypt's population and are regularly the target of Islamist extremists.
Palm Sunday is one of the holiest days of the Christian calendar, marking the triumphant entrance of Jesus to the city of Jerusalem.
There has been no immediate claim of responsibility and the exact cause of the blast is not known.
Previous attacks
In December, 29 worshippers at Cairo's largest Coptic cathedral were killed in a suicide bombing claimed by the so-called "Islamic State" (IS) group.
A number of jihadist-linked attacks and threats against Christians in Sinai have also forced hundreds to flee.
Egypt's army is fighting a counter-insurgency campaign against an IS affiliate in Sinai. Jihadists have carried out scores of attacks against police and army positions.
Islamists have accused Christians of supporting the military and there have been attacks on dozens of churches and Christian properties since Morsi was toppled.
Papal visit
Sunday's attack comes as Pope Francis is scheduled to visit Egypt later this month to show solidarity with the country's embattled Christian community.
The pontiff will also visit Saint Mark's Coptic Orthodox Cathedral which is the seat of Coptic Christian Pope Tawadros II where December's attack took place.
(This article first published on DW. You can read the original article here.)