It broke out around 8 a.m. on Sunday.
Smoke is drifting north from the building for several blocks, blanketing parts of the North End.
The fire is in a two-storey building behind the Staples store, located at 5426 Portland Street.
The building houses the RCR Hospitality Group and Ravensberg College.
Witnesses say flames were shooting from the roof and windows.
"I thought it was the gentleman's smokehouse up the hill there but then all of a sudden we started smelling plastic and the smoke just billowed out," said Jeremy Harper, who lives in the neighbourhood. "She's just coming out of the roof big now."
At least four fire trucks are responding including a ladder truck.
Onlookers are being cleared from the area.
There's no word if anyone has been hurt.