The magnitude-6.0 quake struck at 4:04 a.m., with its epicenter about 35 kilometers (22 miles) north of Bologna at a relatively shallow depth of 5 kilometers (3.2 miles), the U.S. Geological Survey said. Civil defense agency official Adriano Gumina described it as the worst quake to hit the region since the 1300s.
The four people killed were factory workers on the overnight shift when their buildings, in three separate locations, collapsed, agency chief Franco Gabrielli said, In addition, he said, two women died - apparently of heart attacks that may have been sparked by fear. Sky TG24 TV reported one of them was about 100 years old.
Dozens of people were believed to be injured.
Two of the dead were workers at a ceramics factory in the town of Sant'Agostino di Ferrara. Their cavernous building turned into a pile of rubble, leaving twisted metal supports jutting out at odd angles and the roof mangled.
"This is immense damage, but the worst part is we lost two people," fellow worker Stefano Zeni said. News reports said one of the dead had worked the shift of an ill colleague. Elsewhere in the town, another worker was found dead under factory rubble.
In the town of Ponte Rodoni di Bondeno, a worker also died as his factory collapsed, news reports said, citing emergency workers.
Nearly 12 hours after the quake, a sharp aftershock alarmed the residents of Sant'Agostino di Ferrara and knocked off part of a wall of city hall. The building already had been pummeled by the pre-dawn quake, which left a gaping hole on one side of it.
The same aftershock knocked down the clock tower in the town of Finale Emilia, injuring a firefighter. Images from Sky TG24 showed the firefighter lying in the street near the rubble. The national geophysics institute assigned an initial magnitude of 5.1 to the aftershock.
The quake Sunday came as Italy was still reeling from Saturday's bombing that killed one person at a school in the country's south.
Pope Benedict XVI, in his traditional Sunday appearance from his studio window overlooking St. Peter's Square, said he was `'spiritually close" to those affected by the quake, and asked people to join him in prayers for the dead and injured.
Emilio Bianco, receptionist at Modena's Canalgrande hotel - housed in an ornate 18th century palazzo - said the quake "was a strong one, and it lasted quite a long time." The hotel suffered no damage and Modena itself was spared, but guests spilled into the streets as soon as the quake hit, he said.
The fear was palpable in Sant'Agostino. Resident Alberto Fiorini said there was `'pandemonium" during the night.
'I took shelter under the bed and I prayed," he told Associated Press. His house was not damaged, he said.
Many people were still awake at 4 a.m. and milling about town since stores and restaurants were open all night.
The epicenter was between the towns of Finale Emilia, San Felice sul Panaro and Sermide, but the quake was felt as far away as Tuscany and northern Alto Adige. One woman in Finale Emilia told Sky a child had been trapped in her bedroom by falling rubble for two hours before she was rescued.
The initial quake was followed around an hour later by a 5.1-magnitude temblor, USGS said. And it was preceded by a 4.1-temblor.
In 2009, a temblor killed more than 300 people in the central city of L'Aquila, where the historic center is still largely uninhabited and in ruins.