Most of the exterior sculptures have been removed from these cathedral buildings, usually replaced by replica pieces, with the museum conserving the originals.

It occupies the area where much of the sculpture it houses was originally carved, as well as pieces such as Michelangelo's David, which was commissioned for the cathedral (this is now in the Galleria dell'Accademia).

This allowed the construction of large display frameworks copying the architecture of the cathedral, into which the museum's originals are placed at their appropriate positions.

The collection also includes The Deposition, a pietà sculpted by Michelangelo which he intended for his own tomb, and Donatello's wood Penitent Magdalene.

[5] The museum also has significant collections of paintings (mostly late medieval and Early Renaissance), illuminated manuscripts, textiles in the form of vestments, metalwork and church plate, micromosaics and reliquaries.