Smoke and flames could be seen coming from the roof of a home in the 200 block of 37th Street and Memorial Drive Thursday.
Fire crews were called to the vacant building around 11 a.m.
A spokesperson for the Calgary Fire Department (CFD) said the house was boarded up and all utilities had been shut off prior to the fire, but there were signs that people had been inside the house, including a burning mattress.
No one was inside at the time of the blaze and no injuries were reported.
A fire investigator was at the scene for most of the day.
There is no word on what caused the fire.
The CFD is asking anyone with information or video to contact it.