The Trenord train derailed near Pioltello Limito station, under 13 miles outside of Milan, at a switch track.
"There at present are three dead, five extremely injured and eight injured in 'code yellow, ' all of which in doctor's facility", an Interior Ministry in Milan representative told Reuters.
Milan police chief Marcello Cardona told ANSA: "We have identified a failure between wagons, but all the investigations are still under way to clarify the picture".
Firefighters are still trying to rescue several people trapped in one carriage.
Two cars peeled off the rails and came to rest at an angle.
The cause of the accident was not immediately clear.
Emergency services provided helicopters to transport some of the most seriously injured to hospital.
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Italian media quoted witnesses as saying the train began to shake heavily as if it was travelling over rocks.
A statement said: "Service interrupted between Treviglio and Milan due to technical difficulties on an earlier train".
Italy is not a stranger to train crashes.
It was the latest in a number of incidents involving Italy's aging rail system.
The last deadly railway accident in Italy took place in July 2016, when 23 people were killed in a double train collision between Corato and Andria, near the south-eastern city of Bari.
In 2009, some 32 people were killed when a cargo train carrying liquefied gas derailed in the Tuscan city of Viareggio at night, causing an explosion that engulfed the station and some blocks of apartments nearby.