New York State Police say a preliminary investigation determined the crash happened just after 12:30 p.m. on the New York State Thruway as the bus was heading westbound near exit 40 (Weedsport) in the town of Brutus.
Authorites say the bus exited the roadway for an unknown reason and rolled over onto the grassy shoulder.
There were a total of 57 passengers, including the driver, and all were taken to the hospital for injuries ranging from minor to serious.
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The name of the tour bus company is unknown, but police say the bus was headed to the Niagara Falls.
The investigation is ongoing.