Around 4 p.m. MT, the Empire Builder train 7/27 derailed five cars, Amtrak said.
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There were approximately 146 passengers and 16 crew members on board when the incident occurred.
The Liberty County Sheriff's Department confirmed that three people have been killed and the Billings Clinic is calling the accident a "mass casualty" event.
Multiple other injuries were also reported, according to Amtrak, however, the amount and extent of those injuries have not been announced at this time.
"Amtrak is working with the local authorities to transport injured passengers, and safely evacuate all other passengers," Amtrak said in a statement.
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Images from the scene show the train on its side as people gather around it.
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Train #7, which runs between Seattle and Chicago, departed from Union Station at 2:15 p.m. Friday, according to Amtrak's schedule.
The train's route runs along sections of the Lewis and Clark Trail, taking travelers on a nearly two-day ride that ends in the Washington State, Amtrak's website said.
The cause of the derailment is not yet known at this time.
Individuals with questions about their friends and family aboard this train should call 800-523-9101.
"As a result of the derailment, Empire Builder trains 7/27 and 8/28 originating on Sat. Sept. 25 are canceled between Minot, ND (MOT) and Shelby, MT (SBY). Additionally, on Sunday, Sept. 26, westbound Empire Builder train 7 will terminate in Minneapolis, MN (MSP) and eastbound Empire Builder train 8 will originate in Minneapolis, MN (MSP). No substitute transportation is available. Amtrak customers can contact us at 800-872-7245 to obtain additional information about the status of services," Amtrak said.
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Full Amtrak statement:
"We are deeply saddened to learn local authorities are now confirming that three people have lost their lives as a result of this accident. There are also reported injuries among the passengers and crew members traveling on the train. Amtrak is working with the local authorities to transport those who were injured to medical care, and to safely evacuate everyone else at the scene.
"Our Incident Response Team has been initiated, and we are sending emergency personnel and Amtrak leadership to the scene to help support our passengers, our employees and their families with their needs. Individuals with questions about their friends and family aboard this train should call 800-523-9101."
This is a developing story and more information will be provided when it is available.