Flames spread from the third floor up through the top floor of the Fulton Street commercial building just after 2 a.m, eventually shooting through the roof.
One firefighter suffered minor injuries battling the flames, and Fulton Street was closed between Broadway and Nassau Street for firefighting activity.
The cause is under investigation.
The first fire was reported just before 7 a.m. Sunday, and went to four alarms before firefighters brought it under control.
Three firefighters suffered smoke inhalation and were taken to area hospitals Sunday.