Picasso's 1904 "Portrait of Suzanne Bloch" -- from the Spaniard's Blue Period -- and Brazilian painter Candido Portinari's 1939 "The Coffee Worker" were among the Art Museum of Sao Paulo's most important exhibits, the museum said in a statement.
The thieves probably specifically targeted the paintings, which were on display in separate rooms on the second floor, it said.
"We believe that this has the hand of some collector, for his private use," Marcos de Moura, who is heading the police investigation, told a news conference. "This was a professional job, nothing amateur."
Three thieves broke through the main door of the museum just after 5 a.m., then smashed another glass door while an accomplice kept watch outside, de Moura said. They spent only three minutes inside the building.
There was no alarm on either door. Security cameras filmed the break-in but not the exact moment when the paintings were lifted from the walls, he said.
None of the thieves wore a hood, he added.
The museum said it would be closed for the next few days and asked Brazil's Foreign Ministry and the international police agency Interpol for help.