The fire broke out around 5:45 a.m. inside the home on Anthony Avenue in the Tremont section.
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Flames could be seen shooting from the upper floors of the building. It quickly spread to the house next door.
Firefighters used tower ladders and also fought the flames from inside the house. They were inside the occupied house when part of the structure collapsed around them.
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Two firefighters were treated for minor injuries battling what were described as "very treacherous conditions."
Crews are search the debris from the vacant structure, although there are not believed to be any victims.
The cause of the fire is under investigation.
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