The museum, a masterpiece in its own right by the fifteenth-century architect Michelozzo, is a building of first historical importance for the city and contains the most extensive collection in the world of the works of Fra Angelico, who spent several years of his life there as a member of the Dominican community.

The museum also contains other works by artists such as Fra Bartolomeo, Domenico Ghirlandaio, Alesso Baldovinetti, Jacopo Vignali, Bernardino Poccetti and Giovanni Antonio Sogliani.

The oldest section of the building, built over the medieval Sylvestrian monastery, was constructed by the architect Michelozzo at the specific request of Cosimo il Vecchio de' Medici and his expense, to house the reformed Dominicans of Fiesole, an order at that time led by Antonino Pierozzi, the later Antoninus of Florence.

The large room, which can be entered from the right side of the cloister, occupies all the part of the building onto Piazza San Marco and already existed in the Middle Ages when the monastery was inhabited by the Sylvestrian monks.

Basing his work on the preliminaries of rational 15th century classicism, Fra Bartolomeo developed a style of art which was freer in its use of colour space and design and inspired the young Raphael.

The Annunciation is one of the three frescoes painted outside the cells by Fra Angelico (along with Saint Dominic Adoring the Crucifixion and the Sacra Conversazione known as Virgin of the Shadows) before which the friars recited a common prayer at the times and in the ways prescribed by the Dominican Rule.

The cells, larger in size than those of the Fathers to allow the Novices to become gradually accustomed to a reduction in their personal space, all contain frescoes of the same subject, Saint Dominic Adoring the Crucifixion.

From its founding, the nature of the library at San Marco was determined by the decision of Cosimo de' Medici and Niccoli's trustees to establish the collection of bibliophile humanist there.

Under Lorenzo il Magnifico the library became one of the favourite meeting points for Florentine humanists such as Agnolo Poliziano and Giovanni Pico della Mirandola who could conveniently consult the precious book collections assembled by the Medici.

Recent restoration has revealed both the original 15th-century colour scheme, green imitation marble, uncovered "as sample" in a central bay where fragments of a Wind Rose have also been discovered, and some frescoes of architectural illusionism around the doors, probably painted by Iacopo Chiavistelli at the time of the 17th-century renovation of this room.

It was frescoed by Ghirlandaio only about forty years after the construction of the monastery and today contains some glazed terracotta relief works from the Della Robbia studio, dated a little later than the Last Supper.

San Marco met this fate in 1808, returned to Dominican hands after the fall of Napoleon, but then was confiscated in large part by a decree of the nascent Kingdom of Italy dated 7 July 1866 and became State property.

This left to the Dominicans the church, the rooms opening on to the Saint Dominic cloister and the area that came much later to house the library containing over 10,000 books specializing in spirituality, founded in 1979 thanks to the bequest of the Catholic scholar Arrigo Levasti (1886-1973) and named after him.

In 1922 the museum managed to add to its collections a large number of works of Fra Angelico, having them transferred from the Uffizi Gallery or the Galleria dell'Accademia, an arrangement that has since remained unchanged.