On the morning of 11 December 2016, at around 10:00 am, an explosion tore through a chapel adjacent to Saint Mark's Coptic Orthodox Cathedral in Cairo's Abbassia district, during a period when the church compound was hosting worshippers. The blast killed 29 people and injured 47 others. Egyptian state media initially reported uncertainty over whether the device was detonated by a suicide bomber or remotely triggered, though officials believed any remote device would have needed to be large. The device reportedly contained approximately 12 kilograms (26 lb) of TNT, and an unnamed church source told a Nile TV reporter that the bomb had been thrown inside the cathedral's hall near the entrance.
In the aftermath, security forces cordoned off the area, inspected the compound and its security cameras, and the Ministry of Health dispatched fourteen ambulances. Casualties were transported to Demerdash and Dar al-Shifa hospitals. Authorities placed Cairo International Airport and the city's transport network, including its subway, on heightened alert. Prime Minister Sherif Ismail and Cairo's security chief, General Khaled Abdel-Aal, visited the scene, and the prosecutor general ordered Homeland Security to investigate. Cabinet spokesman Ashraf Sultan characterized the attack as "terrorist" in nature. The Interior Ministry also opened an investigation into the police unit that had been assigned to protect the church complex. By 26 December, Egypt's Army Corps of Engineers reported the church renovation was 80% complete, with hopes of reopening it in time for Coptic Christmas on 7 January.
On 12 December, President Abdel Fattah el-Sisi identified the bomber as 22-year-old Mahmoud Shafiq Mohammed Mustafa, reporting that three men and a woman had been arrested in connection with the attack, with two others still being sought. On 13 December, the Islamic State of Iraq and the Levant (ISIS) claimed responsibility via its Amaq News Agency. An Interior Ministry official stated that Mustafa had previously been arrested in 2014 in Fayoum province on charges connected to the outlawed Muslim Brotherhood; a lawyer who represented him at that time described his arrest, subsequent torture allegations, reduction of charges, and eventual release in 2015 after exceeding pretrial detention limits. The Interior Ministry later stated the attack was organized by a group with alleged links to Ansar Bait al-Maqdis (ISIS–Sinai Province), and claimed Muslim Brotherhood figures in Qatar had provided financing — an allegation denied by both the Brotherhood and the Qatari government. By early 2017, eight suspects had reportedly been arrested in connection with the bombing.
The bombing prompted widespread condemnation from Egyptian officials, religious leaders including Coptic Pope Tawadros II and Pope Francis, and numerous governments and international bodies, including the United Nations Security Council, which condemned the attack as an act of terrorism.