Portocarrero began his artistic education at the San Alejandro Academy, but left early and is hence considered 'self-taught'. He put on his first exhibition in 1934, at the Havana Lyceum, beginning a long and fruitful career that included a 1937 collaboration with Mariano Rodríguez and work as a 'free studies' teacher of painting and sculpture. After travels in Haiti, Europe, and the United States he gave his first show to an overseas audience at Julien Levy's gallery in New York City in 1945.

In 1950, he worked with Wifredo Lam, Mariano, Martinez Pedro, and Amelia Peláez in the village of Santiago de Las Vegas. In 1961, he had meetings with Fidel Castro in the Jose Marti National Library, where they discussed culture. René received lessons in painting from Nicolás Guillén Landrián. In 1977 he worked for the Japan Women's Association. In 1979, he worked for UNESCO and AIAP. He knew Peggy Guggenheim.