The Madonna is portrayed on a luminous landscape of hills, on a high throne; in front of her is a pedestal with, on it, a mystic vase, and featuring the signature and date, which were always added by Perugino when the painting was produced in his workshop and then shipped to the destination. Mary holds the Child in the same fashion of the Decemviri Altarpiece of 1495-1496.

At the sides are the saints John the Baptist (with a camel skin and a stick with the cross), Louis of Toulouse, who wears a bishop dress, Francis of Assisi (reading), Peter with the Keys of Heaven, Paul (with a long beard and a red vest) and Mary Magdalene with offerings to the Madonna. The portico is a typical element of Perugino's paintings of the period, such as the Albani Torlonia Polyptych; also typical of his late works is the Madonna's figure as a more mature woman, different than the elegantly youthful portrayal painted before. Less usual are the differentiated proportions of the saints and of the Madonna herself.

The lunette depicts Jesus raised from his sepulchre by Joseph of Arimathea and Nicodemus, with Mary and John the Apostle at the sides. The predella includes the scenes of the Nativity of Mary, the Presentation of Jesus at the Temple, the Marriage of the Virgin, the Annunciation and the Assumption. In these secondary paintings, Perugino used some of his typical themes, including the portico and the oval in a valley.

• Garibaldi, Vittoria (2004). "Perugino". Pittori del Rinascimento (in Italian). Florence: Scala.