The powerful blast, believed to have been caused by a car bomb, injured around 100 others, state media reported.
The explosion took place just after 1am at the regional security headquarters in the Nile Delta province of Daqahliya, collapsing part of the five-floor building.
Most of those killed are understood to have been police officers who were inside the building at the time of the blast.
The explosion reportedly damaged surrounding buildings and wrecked dozens of vehicles.
Security forces cordoned off the area, closed major entrances and exits to the city and set up checkpoints. State TV called on residents to rush to hospitals to donate blood.
Egypt’s interim government accused the Muslim Brotherhood of orchestrating the attack, branding it a “terrorist organisation”.
Prime Minister Hazem el Beblawi expressed condolences to the families of the victims and vowed the perpetrators would “not escape justice”.
The attack comes a day after an al Qaeda-inspired group called on police and army personnel to desert or face death at the hands of its fighters.
It was the first major attack in the Nile Delta, spreading the carnage to a new area and bringing it closer to Cairo.
Previous violence that has killed scores of people has taken place in Sinai or in Suez Canal-area cities such as Islamilia.