[1] A relatively early work, completed in 1469, is the panel of Saints Barbara, Matthias and John the Baptist, painted for the chapel of the German confraternity in the church of the Santissima Annunziata, Florence.

Rosselli was one of the painters called by Pope Sixtus IV to Rome in 1481 to fresco the sides walls of the Sistine Chapel, together with other masters including Sandro Botticelli, Pietro Perugino and Domenico Ghirlandaio.

Giorgio Vasari wrote in his Lives of the Most Excellent Painters, Sculptors, and Architects that, as opposed to the other painters who followed a common pattern in the size and style of the frescoes, Rosselli used brighter colors and a large amount of gold, which granted him the appreciation of the Pope (who, hints Vasari, was not a deep expert of art).

Giorgio Vasari mentioned other works by Rosselli, including the altarpiece of the Madonna and Child in Glory with Saints Augustine and Francis in the third chapel on the left of the nave of Sant'Ambrogio in Florence.

In the same church is the Chapel of the Holy Blood with its frescoes by Rosselli, which Vasari praised highly, especially for a portrait of the young scholar Pico of Mirandola.