Montepulciano is home to some of the most remarkable masterpieces of the Florentine Renaissance. It was a source of inspiration for the subsequent works of classical figurative arts widespread in the Sienese region such as: the tombstone of the humanist Bartolomeo Aragazzi, carved by Michelozzo (a contemporary of Donatello), of which only a few fragments survive in the Cathedral of Santa Maria Assunta.
Many ceramics are displayed in the Della Robbia Civic Museum. Among these are the Madonna of Montecastello altarpiece by Andrea della Robbia (1483-84) and the delicately painted Holy Family with the young Saint John by Sodoma. The church of Santa Lucia houses the beautiful Madonna and Child by Luca Signorelli, characterised by rigorous spatial arrangement. The Temple of San Biagio stands out as a high-point in late-Renaissance architecture, with the construction of this imposing building being supported by Pope Leo X, born Giovanni Lorenzo de' Medici, disciple of Angelo Poliziano. It was completed in 1580.