The central rose window of the façade is decorated with a colossal stained glass window (more than six meters in diameter) depicting the Assumption of the Virgin, created in 1405 by Nicolò di Pietro Tedesco, master glassmaker, on a cartoon by Lorenzo Ghiberti. It is the first of the large series of stained glass windows created for the Cathedral based on Ghiberti's design (thirty in the tribunes and three for the eyes of the dome drum) and also the largest in terms of size and importance, both for the subject depicted, i.e. the glorification of Mary (to whom the Cathedral is dedicated), and for the position, the most visible. The master himself mentions it in his book “Commentaries” "... I drew the Assumption of Our Lady on the face of S. Maria del Fiore in the middle oculus...". The stained glass window was to be the culmination of a cycle with the Stories of the Virgin - never built - for the eight circular windows of the central nave of the Cathedral.

At the center is the Virgin Mary, with hands steepled in prayer, face pointed, enraptured gaze, in a candid dress with floral embroidery. Supported by a pair of Seraphim she ascends to Heaven in a mandorla of glory between two hosts of angels (on the left they hold a scroll, on the right a portative organ). At the apex, framed by golden rays, Jesus Christ descends to crown her. The frame has a motif of Gothic compasses into which, alternating with rosettes, peek out the half-length figures of the twelve Apostles and of two Prophets.

Ghiberti, still young at this time, is stylistically linked to the artists who represented in Florence the so-called "International Gothic" style current: the design is made of vibrant lines, the colors are refined and bright and there is a research of precious details.

The iconography of the Assumption of the Virgin is not derived from the canonical sources of the Gospels but from tradition and hagiographic themes such as the Golden Legend: Mary, after her death, was assumed into heaven with her body. The flowers in the frame and in Mary's dress refer to the name of the Cathedral - Santa Maria del Fiore (“Saint Mary of the Flower”)- that is “Saint Mary of ‘Fiorenza’” (‘of the city of flowers’). The flower is also a Christological symbol: Jesus is the flower bloomed from Mary’s womb.