The central part of the polyptych shows a still archaic style, both in the composition of the frame and in the gold background: Piero della Francesca was in fact called to complete a work already begun by a local painter. Also of lesser quality are the predella panel, which are in fact attributed to assistants. More innovative and typical of the artist's style is the Annunciation, set in a bright cloister, whose illusionist view is considered amongst the greatest perspective renderings of Renaissance art.[1]

The central part of the composition, the Madonna and Child with Staints Anthony, John the Baptist, Francis and Elisabeth, reveals in its unusual damask-like background the artist's aquaintance with a trend of contemporary Spanish painting, which Piero would have had the opportunity to see in Rome. We can therefore date the panel at around 1460. The polyptych is also made up of three predella panels showing St Anthony of Padua resurrecting a child, the Stigmatization of St Francis and St Elisabeth saving a boy who had fallen down a well, as well as two roundels placed between the main panel and the predella. The quality of this predella is extraordinary: Piero's characteristic spatial and light values are achieved here, on a small scale, by emphasizing the white walls of the interiors, the splashes of light and the deep shadows of the night scene in the open countryside. These scenes, where the bodies and even the shadows are fully three-dimensional, were to set an example for predella panels which was widely followed by Italian artists of the second half of the 15th-century, from the young Perugino to Bartolomeo della Gatta and, via Antonello da Messina, to the Neapolitan 'Master of Saints Severino and Sossio'. A few years later, Piero della Francesca completed the Perugia polyptych: above the ornate and still basically Gothic frame, he painted his extraordinary Annunciation.
The lack of compositional unity with the central part of the polyptych has led some scholars to suggest that Piero simply added this Annunciation to the altarpiece, much later.
According to others, the whole polyptych has a structural unity; Piero simply cut out the top part, originally intended to be rectangular, and transformed it into a sort of cusped crowning. Once again Piero has succeeded in overcoming the limitations imposed by patrons with old-fashioned artistic taste, giving us one of the most perfect examples of his use of perspective. Thanks also to his use of oil paints, Piero della Francesca achieves the extraordinarily detailed depiction of the series of capitals, running towards the vanishing point. Each architrave, and each column as well, projects a thin strip of shadow into the splendid cloister arcade, which appears to go beyond any inspiration derived from Alberti's architecture. The subtle analysis of the decorations painted on the walls reaches an unprecedented level; yet everything is contained in a single and organic space. Distances, so perfectly calculated, are neither forced nor artificial: they are conveyed by the realistic light and atmosphere.