The Duomo is the real treasure-house of Montepulciano. It houses many artworks among which emerges the splendid Taddeo di Bartolo's altar piece that towers over the high altar. It is a polyptych, towered and pinnacled, with a splendid double "predella", perfect in every detail, of the Death and Assumption of the Blessed Virgin. In the midst we see the Madonna ravished into heaven, surrounded by angels, while below on the earth the apostles weep for her, since she is gone for them.

There are many figures, and the character of the heads, the wonderfully living and lovely angels, the perfect completeness of the whole work, give to it a beauty and an importance beyond anything else we have from Taddeo di Bartolo.

In the four pilasters are twelve figures of Saints and in the two side panels again other Saints. Above, is the Coronation of the Virgin and on the either side the mistery of the Annunciation. The "predelle" consist of 23 shines concerning the life of Christ and Saints.