The bomb ripped through the multi-storey police headquarters in Mansoura, a city in Nile delta north of Cairo, shortly after 1:00 am (local time), killing at least 13 people and wounding 134, officials said.
"The majority of the casualties are from the police," said Omar al-Shawatsi, the governor of Daqahleya, of which Mansoura is the capital.
Daqahleya security chief Sami El-Mihi was wounded in the blast and two of his aides were killed, security officials said.
The bombing comes ahead of the January 14 referendum on a new constitution seen as the first major step towards democracy after the Islamist president Mohammed Morsi's ouster earlier this year.
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Hours after the bombing, interim prime minister Hazem Beblawi labelled the Muslim Brotherhood as a "terrorist" group, accusing them of orchestrating the attack.
"This is an act of terrorism that aims at frightening the people and obstructing the roadmap. The black hands behind this act want to destroy the future of our country. The state will do its utmost to pursue the criminals who executed, planned and supported this attack," Beblawi told Egyptian TV channel ONTV.
Interior minister Mohamed Ibrahim visited the site of the blast and said Egypt "will not be scared, on the contrary it will reinforce our determination to fight the terrorists".
Meanwhile, The Brotherhood condemned the bombing "in the strongest possible terms", and lashed out at Beblawi.
"It is no surprise that Beblawi, the military junta's puppet prime minister, has decided to exploit the blood of innocent Egyptians through inflammatory statements designed to create further violence, chaos and instability," the brotherhood said in a statement.