At least 12 persons were injured and more than 130 fire fighters were on the scene battling to control the raging flames, a spokeswoman told AFP.
The entire building at 125 Second Avenue was engulfed in angry red flames and the lower two floors appeared partially collapsed, television footage and press photographs showed.
Thick gray smoke spewed over the Manhattan skyline.
It was not immediately clear how many people may have been inside the building, nor how many businesses or apartments it housed. The fire department described it as a mixed commercial-residential property.
The spokeswoman said more than 30 fire units had responded to a “report of a major emergency, possible building collapse and possible explosion.”
“We have heavy fire on the scene,” she said.
In March 2014, eight people were killed when a gas explosion leveled two apartment buildings in Harlem in northern Manhattan. –