The church is built on a longitudinal plan, interrupted by the transept with a lofty space crowned by a cupola at the crossing point and extending into a presbytery towards the apse. The interior immediately recalls Leon Battista Alberti's church of Sant'Andrea. The 1570 earthquake led to alterations, and over time there were other changes. Between 1813 and 1830 the complex was converted into a cemetery. Many details of the liturgical furnishings were lost during the Napoleonic suppression. Also affected was the 1596 altar with its wooden tabernacle, with paintings on copper by Agostino and Ludovico Carracci. Damage caused by bombing during the Second World War was followed by twenty years of reconstruction work.
Attention focused on San Cristoforo once again in 2000 when an agreement was reached between the Monuments departments, the Ferrara Prefecture, municipal and provincial authorities, the Archdiocese of Ferrara-Comacchio and the Cassa di Risparmio's Fondazione to restore and enhance Rossetti's churches.
The renovation aims to restore the interrupted relationship between architecture and decoration, and to return the paintings to their rightful places.