Putatively the church was commissioned in 382 by St Ambrose, to be built along the road that connected Milan (then Mediolanum) to Rome.

Serena, niece of emperor Theodosius I, donated the marbles for the sacellum housing the relics and also embellished the rest of the church.

Also in this age the Romanesque-style octagonal tambour, featuring a circular loggia with small columns, was added over the arms' crossing.

From the left transept, one enters the Chapel of St. Catherine of Alexandria, designed and built circa 1540 by Antonio da Lonate.

In this chapel is a large frescoed arch depicting the Martyrdom of St. Catherine (1548–1549) by Bernardino Lanino[1] and Giovan Battista della Cerva.