First mentioned in documents dating back to the end of the 10th century, the complex was renovated in the mid-13th century by the Vallombrosan Benedictines and again in 1463 at the behest of Bianca Maria Visconti, who married Francesco Sforza in San Sigismondo on 25 October 1441. The 15th-century reconstruction coincided with the establishment of a new monastic order, the Hermits of St. Jerome of the Observance, to whom the duchess was particularly attached. Transformed into a parish church in 1774, the former Gerolamino complex returned to being a monastic seat in 2007, with the arrival of Dominican mothers from the Monastery of San Giuseppe di Fontanellato (PR). 

The church is one of the most significant examples of Cremonese Mannerism, with masterpieces by Camillo Boccaccino, Giulio, Antonio and Bernardino Campi, and of late Lombard Baroque, as demonstrated by the works of Angelo Massarotti, Robert de Longe and Francesco Boccaccino. The refectory, which is open to the public twice a year in accordance with the rules of the cloister, houses the famous Last Supper by Tommaso Aleni, painted in 1508 and one of the first “Lombard” versions to reflect Leonardo's innovations in the Last Supper at Santa Maria delle Grazie in Milano.