It was commissioned for the convent annexed to the church of Santa Maria extra moenia in Messina, also called San Gregorio, whence its modern name.

In 1908, the former convent where the work was destroyed by the 1908 Messina earthquake, leaving its art pieces exposed to the rain which fell in the following days.

The lower level shows, at the center, the Madonna of the Rosary Enthroned, flanked by St. Gregory the Great at left and St. Benedict at right.

There are also trompe-l'œil details, such as the saints' feet which apparently jut out from the step's edge, inspired by spatial innovations by northern Italian painters such as Andrea Mantegna.

He also wears a pendant in red coral, an apotropaic amulet of ancient origins usually given to children, which also appears in contemporary works by Piero della Francesca and other artists.