This mystery thriller is a contemporary adaptation of the renowned Agatha Christie whodunit concerning the death of a malicious American millionaire businessman aboard the Orient Express en route from Istanbul to Paris.

For the dapper Belgian detective Hercule Poirot (Molina), solving murders is a precise, intellectual and often unintentionally humorous exercise. The story begins as Poirot secures a last-minute first class cabin on the Orient Express to Paris. Shortly after the journey begins, an American businessman (Strauss) aboard the train is discovered in his berth, dead from multiple stab wounds. Believing the murderer is still aboard the train, Poirot reluctantly agrees to lend his expertise in solving the crime by sifting through the conflicting clues. In so doing, he interviews the eclectic group of passengers, including Mrs. Hubbard (Baxter), a chatty, opinionated middle-aged woman who turns up clues in the oddest places; Nina Alvarado (Caron), an elderly, formidable, well-traveled name-dropper; and Mary Debenham, a young and beautiful woman with an impeccable British accent who is involved in a secret affair. Although he usually prefers to sift through clues relying solely on the "little gray cells of the brain," Poirot decides to use 21st century technology in his investigation, including a VCR, Palm Pilot, and the Internet via a laptop computer.