The first chapel on the right after the entrance, it houses a cycle of frescoes executed c. 1484-1486 by Pinturicchio depicting the life of the Franciscan friar St. Bernardino of Siena, sainted in 1450.

The frescoes occupy three walls and the vault, and portray the life and miracles of Bernardino of Siena, a Franciscan Friar recently canonized.

The church was in fact held by this monastic order at the time, and the frescoes also include two scenes of St. Francis of Assisi's life.

[7] This fresco shows a more lively composition than Perugino's, both in the figures and the rocks in the landscape, which do not follow a symmetrical pattern and are spatially deeper.

It is one of the first examples of the taste for antiquities which was becoming widespread in Rome at the time, and which was used also by Filippino Lippi in the Carafa Chapel in Santa Maria sopra Minerva.

Under the real window is an illusory opening with five characters: among them is an aged friar, perhaps the convent's prior, and a lay figure that resembles him, perhaps an administrator of the basilica.

[7] Friars, pilgrims and other common people are approaching the corpse to pay homage; on the sides are two richly dressed characters, identified as Riccomanno Bufalini (on the left, with a fur-lined hood and the gloves) and a member of his family.

[7] In the fresco, Perugino's influence on Pinturicchio is manifest:[8] the Umbrian-Perugian perspective rationality, the variety of types and attitudes of the characters, inspired by Florentine painters such as Benozzo Gozzoli or Domenico Ghirlandaio, the striking appearance of the poor pilgrims and beggars, derived from Flemish painting.