The structural analysis of monumental buildings requires to consider safety and conservation objectives, including also the possible presence of artistic assets. In order to face these issues, the paper presents an account of the results of diagnostic analyses conducted by the authors on a specific monumental masonry building: the Civic Museum of Sansepolcro, a small town near Arezzo; in fact, besides to be one of the most renowned civic structures built by Italian communes of Central Italy during the High Middle Ages to house their city governments, it is also characterized by the presence of Piero Della Francesca’s fresco, known as “Resurrection”, that is widely hailed as one of the masterpieces of late 15th-century Italian art. Within th...