The 1965 pencil drawing is called "Tete de Femme," which translates to head of woman. It's valued at $200,000.
The piece was hanging on a column inside the entrance to the gallery. Police say the thief was there just long enough to grab the work and leave. He jumped in a cab and got away.
Gallery owner Roland Weinstein is reassessing his security.
"I feel sorry because it really truly is my goal, and always has been my goal, to be able to bring exactly what you see in this gallery, original works by Picasso, Moreau [and] Chagall onto the street level," said Weinstein. "I want it to be available to the public. We just need to do a better job in the future to make sure our security is in place."
'It's a unique piece, it's something that's high value," said Albie Esparza with the San Francisco Police Department. "So we're hoping it will turn up very quickly soon somewhere."
Investigators say the preppy looking thief is six feet tall, about 30-35 years old. He was wearing a dark jacket, white shirt, dark pants and loafers without socks. Anyone with information in this case is asked to call the SFPD.