The modern use of ancient heritage sites can be, to say the least, challenging from an acoustical perspective. In fact, modern needs may require acoustical interventions in contrast with the preservation issues of the cultural heritage. This paper deals with this topic in an UNESCO designated world heritage site, the Palatine Chapel of the Royal Palace in Caserta, Italy. Since this chapel is currently being used for meetings and music chamber concerts, the acoustical characteristics of the chapel, originally used for religious purposes, are investigated. Field measurements were undertaken to evaluate the acoustical performance of the empty chapel. The measurements were then used to calibrate and validate a computer simulation model. Different acoustical treatments are then considered and simulations are used to determine the related acoustical improvements. Finally, the benefits of different acoustical treatments which are respectful of the aesthetic and historical value of this cultural heritage are discussed.