The works of the Perugian Renaissance school are very similar and often paintings by Perugino, Pinturicchio, Lo Spagna, and a young Raphael may be mistaken, one for the other.

His assignment in Rome, to decorate the Sistine Chapel, was an experience fraught with learning from prominent artists of the time, including: Sandro Botticelli, Domenico Ghirlandaio, Pietro Vanucci, and Luca Signorelli.

[2] Pinturicchio's fresco, Assumption of Mary, executed in 1481 on the altar wall of the Sistine Chapel, was destroyed in 1535 to make way for Michelangelo's Last Judgement.

Critic Evelyn March Phillipps sums up his work by saying that the basilica "[w]ould be if it had been left with all its original decorations, one of the finest monuments to Pintoricchio’s art in Italy.

The polychrome grotesque wall decoration on a yellow-gold background probably was inspired by the paintings of the Domus Aurea, and belongs the earliest and highest quality of their kind in Rome.

The Basso Della Rovere Chapel contains a fine altarpiece, Madonna enthroned between Four Saints, and on the eastern side a very nobly composed fresco of the Assumption of the Virgin.

[2] Among other important frescoes by Pinturicchio that still exist in Rome and are in good condition, are in the Bufalini Chapel in the southwest sector of Santa Maria in Ara Coeli, probably executed around 1484–1486.

On the altar wall is a grand painting of St. Bernardino of Siena between two other saints, crowned by angels; in the upper part is a figure of Christ in a mandorla, surrounded by angel musicians; on the left wall is a large fresco of the miracles performed by the corpse of St. Bernardino, which includes portraits of members of the sponsoring Bufalini family.

The composition of the main group around the saint's corpse appears to have been suggested by Giotto's painting of St. Francis on his bier that is found in Santa Croce at Florence.

Another fine altarpiece, similar in delicacy of detail, and probably painted about the same time, is that in the cathedral of San Severino — the Madonna enthroned looks down toward the kneeling donor.