Officials said several people were trapped under the rubble of houses and warehouses in the Emilia-Romagna region, where several building sites and workshops had just reopened after the previous quake on May 20.
Civil protection officials said 15 people were confirmed dead. S even people were killed in the May 20 quake that, like Tuesday's, had its epicentre not far from the city of Modena.
Italian television showed buildings shaking and collapsing, ambulances racing across towns and rescue workers battling to remove rubble.
Workshops and factories outside Cavezzo, a village about 30 km (20 miles) from Modena, suffered considerable damage, a Reuters reporter said.
Sports car maker Ferrari and motorcycle firm Ducati closed their plants in the region for safety reasons.
"The situation is one of great fear and uncertainty," said Salvatore Iannizzotto, provincial head for the Modena police.
"The population was becoming more relaxed and slowly moving back into their homes. They have now left their homes again."
The 5.8-magnitude quake was felt across northern and central Italy, including in the most populous northern city Milan. The area was hit by several large aftershocks, one of 5.6 magnitude.
The quake was the most deadly to strike Italy since 2009 when a tremor partially destroyed the central city of L'Aquila, killing about 300 and leaving thousands homeless.
Emilia-Romagna, famed for its cured ham and mature Parmesan cheese, is in the middle of the Po plain, traditionally considered safer than other areas of seismic Italy.
Several historic buildings, some damaged by the previous quake, suffered further damage.
"We are all in the streets, there are people crying with fear. It seems like a nightmare but it's all true," said one Twitter message.
In the town of San Felice sul Panaro, about 30 km from Modena, which saw its imposing 14th-century Estense Castle badly damaged in the previous quake, three workers were killed by a crumbling warehouse.
"The situation is very serious, some people are stuck under the rubble," Alberto Silvestri, the mayor of San Felice sul Panaro, to ld SkyTG24.
Prime Minister Mario Monti tried to reassure the population in an impromptu news conference.
"I want to assure everyone that the state will do all that it must do, all that is possible to do, as fast as it can to guarantee the return to normality in a region so special, so important, so productive for Italy," he said.
The quake risks further damaging Italy's economy, which is struggling with recession. Farmers estimated the damage of the previous quake to agriculture in one of Italy's most fertile zones at more than 200 million euros.
On Tuesday, officials said rescue operations had been hampered by disruption to the mobile phone network.
"The town has been largely damaged. There are people under the rubble, we don't know how many," a police officer from Cavezzo told Reuters.
Giulio, a 72-year-old resident of Cavezzo, said: "As we were coming down the stairs, we heard the sound of crumbling houses around us. There was a big dust cloud. The town is being evacuated."
Train services around Bologna, near Modena, were temporarily disrupted, media said, and schools and other public buildings had been evacuated as far south as Florence.
French President Francois Hollande's office said France stood ready to provide Italy with any experts or logisitical aid it might need.
A 3.8 magnitude earthquake was also felt through western Bulgaria on Tuesday, causing no casualties or serious damage, the National Geophysical Institute said. The tremor had its epicentre near Pernik, shaking buildings and causing residents to rush into the streets.