The fire was reported at a bakery on Starlight Street just after 3 p.m.
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RELATED: 4-alarm fire on Sign Hill in South San Francisco fully contained, evacuations still in place, officials say
South San Francisco firefighters and law enforcement are at the scene.
The fire appears to be put out, but firefighters are still there making sure there are no remaining hot spots that could flare up.
No injuries have been reported.
Officials are asking the public to avoid the area until further notice.
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This comes on the heels of a fire on the city's famous Sign Hill the same afternoon.
Stay with ABC7 News for the latest details on this developing story.