The tanker was believed to be carrying liquefied petroleum gas.
The tanker truck was carrying flammable materials on a highway in the area of Borgo Panigale in northern Italy.
A police video showed the tanker failing to slow down and plowing into the back of a truck that was stopped in traffic.
A motorway bridge has also partially collapsed in a huge explosion which shook Bologna Airport in Italy.
The crash, near the airport in Bologna, caused part of a bridge to collapse, with several vehicles in a auto park below it catching fire and exploding.
The tanker truck's driver was killed, but two highway patrolmen were credited with preventing more deaths by clearing the road of startled and curious motorists in the minutes between the collision and the blast. The road had been cleared by this point, but still, scores were injured.
Among the injured are eleven military police officers.
"More than 60 people were injured. some seriously", Deputy Prime Minister Luigi di Maio wrote on Twitter.
Numerous victims had been hit by flying glass when windows in nearby buildings exploded, a local television network reported.
Bologna is the lively, historic capital of the Emilia-Romagna region, in northern Italy. Video and photos from witnesses showed a massive fireball shooting into the air on a highway in the suburbs of Bologna on Tuesday afternoon.
Sky News reported that it took three hours for the flames to be fully extinguished. "Numerous injured received cuts from flying glass, which had shattered", said Giovanni Carella, the emergency coordinator for the local fire service.