The initial structure on the site of Vigevano Cathedral was built before the year 1000 and is referred to in documents of as early as 963 and 967.
The current structure was commissioned by Duke Francesco II Sforza in c. 1530 and is dedicated to Saint Ambrose. Construction on the cathedral, designed by Antonio da Lonate (c. 1456–1541), began in 1532 but was not completed until 1612. The edifice of the cathedral was completed in 1606 and it was consecrated on 24 April 1612.
The Spanish Cardinal Juan Caramuel y Lobkowitz was hired to redesign the west front of Vigevano Cathedral, work which began in 1673 and was completed c. 1680. The only architectural work known to be done by Lobkowitz, his design displays virtuosity, eclectivity, and an interesting geometrical relationship to the square which is cleverly adjusted to bring the ancient cathedral into a line perpendicular to and centered on the axis of the piazza.
The interior is designed on the Latin cross plan, with the nave containing a central aisle and two side aisles, and houses works by Macrino d'Alba, Bernardino Ferrari and others, as well as a tempera polyptych of the school of Leonardo da Vinci.
The cathedral is best known for the 'treasury' donated to it by Francesco II Sforza in 1534 which encompasses more than 100 precious objects. These, along with other items, are on display in a museum inside the cathedral known as the Museo del Tesoro del Duomo Vigevano. Of note in the collection are several Flemish tapestries, seven of which were made by tapestry makers in Brussels in 1520 in the Late Gothic International Style and five of which were woven in Oudenarde at the beginning of the 17th century. Also on exhibit are an ornate crosier in ivory, a gold-plated silver reliquary of the Lombardy school of goldsmiths from c. 1530, numerous precious corals, missals, codices and manuscripts dating from the late 15th century, and many chalices, goblets, monstrances and reliquaries in different styles and from different eras.
Also of interest is a 16th-century wall-hanging embroidered in gold which was used in Monza in 1805 for the coronation of Napoleon Bonaparte.
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