EL2, local analysis and EL3, global analysis), according to an increasing level of knowledge on the building. A comprehensive knowledge process, composed by a 3D survey by Terrestrial Laser Scanning (TLS) and experimental in situ tests, allowed us to identify the basic structural geometry and to assess the value of mechanical parameters subsequently needed to perform a reliable structural assessment. The museum represents a typology of masonry building extremely diffused in the Italian territory, and the assessment of its seismic behavior was performed by investigating its global behavior through the EL1 and the EL3 analyses This paper reports the knowledge process and the analyses performed to assess the seismic behavior of a heritage masonry building. The case study is a three-story masonry building that was the house of the Renaissance architect and painter Giorgio Vasari (the Vasari’s House museum). An interdisciplinary approach was adopted, following the Italian “Guidelines for the assessment and mitigation of the seismic risk of the cultural heritage”. This document proposes a methodology of investigation and analysis based on three evaluation levels (EL1, analysis at territorial level