The blaze broke out at 3 a.m. Friday in the 1000 block of South Broad Street.
Crews arrived to find flames shooting from the second and third floors.
The back of the house had collapsed.
"The fire building was a vacant structure," said Trenton Fire Dept. Battalion Chief Todd Willever. "The attached exposures were both occupied, and both evacuated safely. All occupants evacuated."
Firefighters declared the blaze under control in less than an hour.
There were no reports of injuries.
Fire investigators were working to pinpoint the cause.
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