A church has stood on the site since 726 with the present building dedicated to Saint Cassian of Imola being consecrated in 1376 and re-modelled during the 17th century.

The church is located on the Campo San Cassiano, site of the world's first public opera house, west of the Rialto Bridge and is open to visitors Tuesday-Saturday mornings.

[2] In 1509, the funeral procession of Catherine Cornaro, the former queen of Cyprus and wealthy Venetian noblewoman, began at San Cassiano.

A feature which may possibly have been retained from the original church is the door jambs or doorposts, which date back to the Byzantine era.

[3] In 1746 Abbot Carlo del Medico commissioned a chapel which is located on the left-hand side of the church.

[4] The Sicilian artist Antonello da Messina was commissioned by Pietro Bon to paint an altarpiece for the church.

[6] It brought a style of altarpiece that would be imitated by other Venetian artists such as Giovanni Bellini, Giorgione and the Vivarini brothers, Antonio and Bartolomeo, establishing a template that would be used all the way through to Titian.

[6][7] San Cassiano's altarpiece disappeared from the church sometime during the 17th century and reappeared in the private collection of the Austrian Archduke Leopold William where it was attributed to Giovanni Bellini.