Emergency services workers search the wreckage for trapped passengers.
In photos, three carriages are sprawled across the tracks, one of them tilted to the side, smashed into a pole.
Over 100 sustained light injures, according to regional emergency official Cristina Corbetta.
She said the incident happened at around 7 am (0600 GMT) near Segrate in Milan's northeastern suburbs.
It is not clear what caused the train, operated by Trenord, to come off the track.
Numerous passengers were travelling to work in Italy's economic capital, or were students.
Television images showed injured survivors being evacuated, the more serious receiving first aid in a field close by.
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One of the injured could be seen, clothes ripped, covered with a thermal blanket and wearing an oxygen mask being evacuated by helicopter.
Waiting medics then strapped some to stretchers and rushed them to hospital - while those with less severe injuries sat by the tracks and called loved ones to let them know they were alive.
The train was headed for central Milan from Cremona with hundreds of commuters on board.
A number of rail services in Milan, Italy, have been delayed or suspended in view of the Milan train derailment.
Prosecutors rushed to the scene alongside firemen and police, questioned the train driver and opened an investigation into the accident.
Trenord, a local train organization serving the Lombardy area, has a famous reputation among riders.
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