Raffaellino was a pupil of Raphael, whom he is held to have assisted in the decoration of the Farnesina and of the stanze in the Vatican Palace.
After Raphael's death, Raffaellino continued working in the Vatican, helping complete the Sala di Constantino though now under the direction of Giulio Romano.
After the 1527 Sack of Rome, like most of Romano's studio and most of the foreign art community, Raffaellino and other artists dispersed through Italy, most returning to their home cities.
Rafaellino went to Città di Castello, near his birthplace, where he painted altar-pieces for the principal churches, which are now mostly to be found in that town's Municipal Art Gallery.
In 1536, Vasari commissioned from Raffaellino some ephemeral street decorations to celebrate the entry of Charles V into Florence.