At least two people were killed and more than 60 injured, according to local authorities.
Police closed off the road where the crash took place as well as the surrounding area of Borgo Panigale, on the outskirts of the city of Bologna.
Video of the incident showed the tanker truck, which contained inflammable materials, slamming into the back of a lorry which had come to a halt because of heavy traffic.
The tanker immediately caught fire and then exploded, causing part of a road bridge to collapse.
The fire spread to a car dealership below and several other vehicles burst into flames.
“The shockwave from the blast was extremely violent. Many of the injured received cuts from flying glass, which had shattered,” said Giovanni Carella, the emergency coordinator for the local fire service.
He said he thought the tanker had probably been carrying liquid petroleum gas.
A video shot from a parked car appeared to show someone being engulfed by flames when the tanker exploded.
In a separate incident on Monday, 12 migrant labourers died in the southern Italian region of Puglia when the van they were travelling in smashed into a lorry.