Police say attempts were made to revive her, but she was pronounced dead after being rushed to hospital.
The exact cause of death is not yet known — police said only that the girl suffered a medical emergency.
Police didn't reveal her name, but the Cape Breton Post identifies the teen as Emma van Nostrand, a Grade 12 honour student at Riverview High School in Cape Breton.
Another runner, a man, also collapsed during the race but bystanders and paramedics were able to resuscitate him and he was later reported to be in stable condition.
Before the race runners paused for a moment of silence to honour the victims of the Boston Marathon bombings. Runners also wore bibs featuring a toonie-sized "Remember Boston" ribbon image.
Terry Gehl of Saint-Charles-sur-Richelieu, Que., took the men's title finishing the 42.1 kilometre course in two hours 37 minutes 30.1 seconds.
Montreal's Mylene Sansoucy won the women's title crossing the line in just over two hours and 58 minutes.
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