The Cathedral of Orvieto is one of the most significant monuments representative of the Roman architecture of the late XIII century in Italy. The architectural configuration consists of three principal corpus (structural macro-elements): the magnificent tricuspid facade, the main nave and a massive transept. They have different masses and stiffness and dynamically interact each other. The columns of the central nave are one of the critical elements of the whole monumental complex; their cracking pattern has been identified by means of high resolution photogrammetry imported and superposed to vector drawing CAD and each crack has been taxonomically identified. The measurements have been integrated by non-destructive investigations of sonic tomography and prospecting radar to evaluate the mechanical properties of the materials of the columns for the evaluation of the seismic vulnerability. Furthermore, a thermograph image restitution of the walls of the nave defined the degradation zone. This study is being executed within the agreement between the "Italian National Agency for New Technologies, Energy and Sustainable Economic Development-ENEA" , the "Ministry of Heritage and Cultural Activities -MIBAC" and the "Opera del Duomo di Orvieto". © 2015, International Society for Structural Health Monitoring of Intelligent Infrastructure, ISHMII. All rights reserved.