Crews responded to reports of fire at a home at 26890 Alejandro Drive at about 11:30 a.m., the dispatcher said.
A fire official said the blaze appears to have started on the second floor.
No injuries have been reported, the dispatcher said. He said at 12:30 p.m. that the fire had been mostly controlled.
A resident who lives across the street said the neighborhood was smoky.
He said it appears the fire damaged the upper floors of the single-family home, and that there were at least six fire trucks on his block.
Palo Alto fire crews were assisting in the response.