The fire was first reported at around 5:00 p.m. at the store.
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No injuries were reported to fire personnel or citizens from the incident, according to San Jose Fire Department.
A shelter-in-place remains in order for residents in certain areas due to drift smoke, the department tweeted. They say that the air quality is deemed unhealthy by the hazardous team members, and to be reevaluated in the morning.
ABC7 News reporter Dustin Dorsey says the thick smoke can be seen from miles away in Santa Clara County. It's even seen from outer space, NWS Bay Area tweeted.
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A pet hospital near the area had been evacuated with dozens of pets transported.
As for the cause of the fire- officials say it's likely a long way out from knowing.
"The Home Depot is pretty much a total loss, the roof is pretty much collapsed from the entire structure so it's going to take some time to get in there if we even can- if it's going to be safe for our people to get in there," said SJPD battalion chief Brad Cloutier.