Italy's Civil Protection Authority confirmed 15 people had perished and rescue forces were searching for four or five other people still missing after a series of strong quakes which caused widespread panic among residents.
"I have to leave the building, we're being hit by a long, powerful tremor. I have to get out," a civil protection agency spokesman in Mantua told AFP.
Authorities said the region was struck between 1056 GMT and 1101 GMT by three tremors of between 5.1 and over 5.3 magnitude, following a 5.8 magnitude quake just after 0700 GMT when people were heading into work.
"Everything's collapsed, it's chaos, buildings across the town are down," a fireman in the tiny town of Cavezzo told Corriere della Sera newspaper.
The first quake struck about 60 kilometres (40 miles) east of Parma, according to the Geographical Institute of Modena, and sent panicked residents rushing into the streets in quake-struck cities including Pisa and Venice.
Tuesday's quakes followed a 6.0 magnitude quake in the industrial northeast on May 20 which killed six people and left thousands in makeshift tent dwellings, with many homes and historic buildings reduced to rubble.
"Everything was shaking, we ran out into the streets. The roads are now blocked by people trying to flee the centre in case there's an aftershock," Corriere della Sera reporter Elvira Serra said from the small town of Cento.
Historic chapels, churches and buildings damaged in the first quake crumbled to the ground as panicked citizens joined those already camping out in blue tent camps set up in parks and school playgrounds after the last quake.
Over 5,000 people were evacuated from their homes and emergency places for 4,000 homeless would be ready by nightfall, the Emilia Romagna region said.
"Last night was the first night we'd spent back in our homes after the first quake. Then another one hit," one resident told SKY TG24 television in Sant'Agostino, scattered with buildings with gaping holes in their sides.
Several victims were workers crushed when factories collapsed, while a parish priest in the town of Rovereto di Novi was killed by a falling beam, reportedly after he went back into his church to save a Madonna statue.
In San Felice del Panaro, the dead were identified as Italian, Moroccan and Indian factory workers. "I don't think we are safe, the factory has completely collapsed," a fellow Indian worker told AFP as he called on Allah for help.
Dust filled the air in the picturesque towns of Carpi and Concordia, while in Mirandola rubble covered the Duomo floor and the roof gaped open to the sky.
In Mantua, the Ducal Palace -- famous for a stunning collection of frescoes in the Wedding Room -- was damaged, along with a number of historic churches.
"A new quake has hit the Emilia Romagna region, leaving victims, wounded people and damaged buildings in its wake," Prime Minister Mario Monti said earlier Tuesday in a televised address from Rome.
"I send the government's condolences to the families of the victims and call on all citizens to have faith. I'm sure we'll get over this moment," he said.
Tuesday's quake was felt throughout northern and central Italy, causing the the collapse of houses and schools structures weakened by the quake nine days ago.
"The population hit will not be abandoned," said the head of the Emilia Romagna region, Vasco Errani.
In Pisa, home of the famous leaning tower, offices were evacuated as a precautionary measure. People ran out into the streets from shops and offices in Milan, Bologna and the Aosta Valley, close to the French border.
There were moments of panic in Venice, where a statue fell to the ground, lightly injuring a passerby.
Around 7,000 people who fled their homes in northeast Italy in the quake over a week ago still living in around 89 tent camps erected in fields, sports fields, car-parks and schools, which can take up to 9,000 people.
The region has been hit by a series of quakes and aftershocks over the past two weeks. Authorities have registered at least 800 tremors since May 20.
The latest disasters struck just over three years after a 6.3-magnitude quake devastated the city of L'Aquila in central Italy in March 2009, killing some 300 people and leaving tens of thousands homeless.