Architect Giovanni Battista Bertani built the palatine church in a small square inside the enormous ducal palace, on the orders of duke Guglielmo Gonzaga (1550-1587). The building started in 1561 and finished in 1572, while the bell tower was completed in 1565. 

In the same year, Pope Pius IV accorded a college of canons and its own liturgy to the basilica. Duke Guglielmo let make precious reliquaries (now at the Diocesan Museum) to preserve the saints' relics he acquired. In 1565 Graziadio Antegnati made the organ, and the duke gave the basilica a prestigious musical chapel (De Wert, Palestrina, Gastoldi).

The façade is Mannerist; the interior is suffused with the light coming from two lanterns on the nave ceiling. A spiral staircase takes from the elevated presbytery to the crypt, which is a peculiar three-naved elliptical room. You may appreciate the altar piece by Domenico Brusasorci (1564) depicting St. Barbara's martyrdom, the organ panels by Fermo Ghisoni (1566) depicting the Annunciation – while they depict St. Barbara and St. Peter when they are shut -, two great canvases by Lorenzo Costa the Younger depicting the baptism of Constantine (1571) and St. Adrian's martyrdom (1570) – they were both cartooned by Bertani. Behind the first altar on the left you can admire the Baptism of Christ by Teodoro Ghisi, then the Washing of  the Feet by Ippolito Andreasi. On the right side, you can see the Delivery of the Keys and St. Margaret of Antioch by Giovanbattista Giacarelli (1572). 

Finally, in the first chapel on the left side, you may see a canvas by Giuseppe Bazzani (mid XVIII century) depicting the Madonna and Child with St. Aloysius Gonzaga and St. Margaret.