The robbery was reported at about 11:15 a.m. at a bank in the 500 block of Montgomery Street.
The suspect, a man in his 40s or 50s, walked into the bank, took out a handgun and demanded money from a 56-year-old employee, according to police.
The female employee handed over an undisclosed amount of cash to the suspect, who fled from the bank and had not been found as of this morning, police said.
No one was injured during the robbery.
Anyone with information about the case is encouraged to call the Police Department's anonymous tip line at (415) 575-4444 or send a tip by text message to TIP411.