Santo Spirito is a church whose current edifice is largely a reconstruction from 1498-1504. 
It has a notable Renaissance portal by Baldassarre Peruzzi, while the interior houses numerous artworks. These include works by Il Sodoma in the Spaniards Chapel, a canvas with the Miracle of St. Hyacinth by Francesco Vanni in the right transept surrounded by frescoes of Ventura Salimbeni, a rare terracotta nativity scene by Ambrogio della Robbia, Four Saints by Rutilio Manetti (pilasters flanking the high altar) and, in the apse, a Pentecost by Giuseppe Nicola Nasini.

In the sacristy, located where once was the cloister, is a 1516 fresco by Fra Paolo da Pistoia.