The pen-and-ink drawing, believed to be called "The Judgment," was nabbed Saturday night while a curator was distracted by a guest at the Ritz-Carlton Hotel in Marina del Rey, Los Angeles County Sheriff's spokesman Steve Whitmore said Sunday.
Detectives believe the theft occurred during a 15-minute window starting at 10:20 p.m.
"When the curator turned back to the Rembrandt, it was gone," Whitmore said, adding that it "was a well-thought-out, well-executed theft."
Investigators were studying surveillance video from the hotel. The footage was unlikely to be made public, Whitmore said.
Officials asked anyone who spotted anything suspicious to contact the sheriff's department. Sheriff's detectives were working with security officials from the hotel.
"The Ritz-Carlton has some of the best hotel security in the nation," Whitmore said. "We're confident that our leads, and the surveillance video will help us solve this."
Whitmore said the work by the Dutch master was valued at $250,000.
The drawing was part of an exhibit at the hotel sponsored by San Francisco's Linearis Institute. A call to the institute was not immediately returned Sunday.