The crime was the third burglary of a downtown jewelry store in the last two months, Los Altos police Detective Sgt. John Korges said.
However, since the latest burglary was more sophisticated, investigators do not believe it is related to the others, Korges said. The burglary happened early Sunday morning at Harold's Jewelry at 164 Main St., which is equipped with an alarm.
Someone forced entry into an adjoining business that did not have an alarm and then broke into the jewelry store by smashing through a common wall, Korges said.
He said that, due to the amount of labor the burglary required, it appears more than one person was involved.
Once in the jewelry store, the suspect or suspects used commercial-grade tools to penetrate the safe, taking between $350,000 and $400,000 of loose precious stones and jewelry left for service and repair.
Officers eventually responded to a commercial burglary alarm at the jewelry store but did not locate a suspect.
Korges said the two previous burglaries downtown appeared to be "crimes of opportunity."
Police did not have a suspect description.
Anyone with information on the case is asked to call Korges at (650) 947-2770.