The painting was commissioned to Cosimo Rosselli in April 1470 and was placed as an altarpiece in a chapel dedicated to Saints Anthony Abbot and Nicholas, founded between 1462 and 1468 by the testamentary will of Mariano di Stefano Nese, in the church of San Pier Scheraggio. The building, which still exists today, was incorporated by Vasari into the architectural structure of the Uffizi. The painting is one of the oldest known works by Cosimo Rosselli, who was trained in the workshop of Neri di Bicci, where he spent three years, from 1453 to 1456. Like his master, the artist prefers traditional and consolidated models in the artistic repertoire of the time: the curtains of cloth that “open” the scene, already widely used by Alessio Baldovinetti; the marble floor derives from the one painted by Pollaiolo for the Pala del Cardinale del Portogallo in San Miniato al Monte, a few years earlier (and now in the Uffizi); the standing Child recalls the marble reliefs by Desiderio da Settignano. In the construction of the sacred scene, the perspective converges strongly towards the centre, accentuated by the figures in the foreground placed in three-quarters and by the pillars of the throne, which squeeze towards the bottom. The figure of Mary emerges clear and bright, affectionately holding the Child to herself, while with a thoughtful and melancholy look she seems to foresee the future.
To the left of the viewer is Nicholas, the saint who lived in Lycia and was elected bishop in 300 AD, whose relics arrived in Bari in 1087. He is identified by the three golden balls he holds in his right hand, representing the act of mercy he performed: the donation of a bag of gold coins to a man who could not afford to make a dowry for his three daughters. On the right is St. Anthony Abbot, the famous hermit of the Church, who was born in and lived in Egypt, here represented with a long beard (he died over a hundred years old in 353 AD), with a tau-shaped stick (sign of Christian devotion, last letter of the Hebrew alphabet and representation of the cross) and a small pig. This typical attribute of the Saint is connected to various traditions, one of which would see the use of the fat of the animal as a remedy for shingles, also known as St. Anthony's fire: the saint was also venerated as protector of this disease.
Cosimo Rosselli had excellent entrepreneurial skills and, like his master, was at the head of a large workshop of artists, thanks to which he was able to diversify his commissions: from panels, to wall paintings, to the realisation of apparatuses and more. Under him were formed for example Piero di Cosimo and Baccio della Porta.
The work came into the grand-ducal collections following the suppression of ecclesiastical institutions promoted by Pietro Leopoldo of Lorraine in 1784.