In the same place as the present Renaissance building, there used to be three churches built in the fourth century and dedicated to Christ the Saviour, to Saint John the Baptist and the Virgin Mary. The liturgical space dedicated to the Baptist, who initially served as a baptistery, was enlarged

After demolishing the three pre-existing churches, the cathedral was rebuilt between 1491 and 1498 for Cardinal Domenico della Rovere, bishop of Turin but residing in Rome at the Papal See. The work was entrusted to a Tuscan architect already active in Rome, Amedeo da Settignano also called Meo del Caprina,