It happened at the Institute of Molecular Medicine located at 1825 Pressler Street between Fannin and Main around 9:40 p.m.
Plastic from the sign's letters on fire dripped to the lower mezzanine level.
While the fire didn't spread to inside of the building, it's air handling system did suck in smoke, requiring the Houston Fire Department to ventilate it.
According to HFD, the building was closed, but one person was inside at the time.
No one was injured.
The cause of the fire is under investigation, but fire officials say they believe it is electrical due to the sign. It was not weather-related, HFD said.