This fresco depicts the two last episodes from the story of the life of Peter: to the right we see him, with St Paul, in his dispute with Simon Magus in front of the Emperor; to the left, his Crucifixion.

On the right, outside the city walls (in Rome, as indicated by the Pyramid of Cestius along the Aurelian Walls and by the edifices peeking from the merlons), one may see the disputation between Simon Magus and St Peter in front of Nero, with a pagan idol lying at the latter's feet. On the left, Peter's crucifixion is taking place: the saint is hanging upside down because he refused to be crucified in the same position as Christ's.

The two episodes are replete with portraits: the youth with a beret on the extreme right is Filippino's self-portrait. The old man with a red hat in the group near St Peter and Simon Magus is Antonio del Pollaiolo. The young man below the archway and looking towards the viewer is a portrait of Sandro Botticelli, Filippino's friend and teacher. In Simon Magus, some critics wish to see the poet Dante Alighieri, celebrated as the creator of the renowned Italian vernacular used by Lorenzo il Magnifico and Agnolo Poliziano.

Recently it was suggested that Masaccio had originally painted the last scene of the cycle, the Crucifixion of Peter. But that fresco was then destroyed when the Madonna del Popolo was placed on the altar so that when Filippino Lippi was called in to complete the unfinished cycle and repair the damaged sections, he was also asked to add the scene of the death of Peter on the empty wall space.