Florence (Italy) is a worldwide well-known cultural historical city, with many outstanding monumental buildings visited every year by about 20M people, since 1982 the historical city center is under the UNESCO Patronage. Conservation of monumental buildings is subject to the principles of integrity and authenticity, in Italy recalled by the Ministry for Cultural Heritage 2011 rule, which defines the procedure for their seismic vulnerability evaluation. For that, the knowledge of the masonry structure is in need, and in lack of historical documentation on the design, only non destructive tests (NDT), or very low destructive tests, can be run on the masonry for acquiring this knowledge on its structure and consistence. For this purpose, we are largely using specific ground penetrating radar (GPR) technology, which is resulting highly performing in defining masonry structure and consistence. This paper summarizes selected case histories regarding the main Florentine historical monumental buildings: Palazzo Vecchio, Brunelleschi's Cupola, Giotto's Bell-Tower, and San Giovanni Baptistery. The correct interpretation of the GPR data requires knowledge about the masonry techniques of the age of construction, and local verification with micro drill-holes with video inspections, sonic and ultrasonic tests, in defining historical monumental buildings masonry structure and competence, static and dynamic behavior parameters and seismic vulnerability.