About 100 other people sustained light injuries, Cristina Corbetta, an official with the regional emergency services in Milan, told Sky TG24.
She said the incident happened at around 7 am near the Milan suburb of Segrate. The cause was not immediately clear.
Two hours after the tragedy, rescuers continued to search the inside of the cars, at least two of which lay on the track, in search of trapped passengers.
A journalist for Sky TG24 at the scene said five or six people were still trapped inside.
Television images showed injured survivors being evacuated, the more serious receiving first aid in a field close by.
Only the cars in the middle of the train derailed.
The regional train was enroute from the town of Cremona to the centre of Italy's economic capital.
It is the most serious rail accident in Italy since 23 people were killed in a high-speed head-on collision between two passenger trains in July 2016 in the southern Puglia region.