The coach reportedly crashed into a truck on the A9 near Muenchberg in southern Germany just before 7am (local time).
Police say 31 people are injured and 17 people are unaccounted for.
Reports suggest the coach is completely burnt out.
A police spokesman in Bayreuth said: “We have to assume that it was a very serious traffic accident.
“The fate of the other passengers is currently the subject of police action on the ground.”
The A9 has been completely blocked off to the south, a police officer said.
According to reports, the coach was travelling from the north towards Nuremberg when it allegedly drove into the back of a slow driving artic close to Münchberg.
The coach was carrying 46 passengers and two drivers.
Emergency services, including a rescue helicopter, are currently on the scene.
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