It has become a common practice to include diagnostics and archaeometric studies during a masterpiece restoration. The advantages and limits of this approach are now topic of discussion in the community of researchers that is growing up quickly. The bronze burial monument of Pope Sixtus IV (1471–84) by Antonio del Pollaiolo, now in the Treasure Museum in the Vatican was intended to be located at the center of a chapel, this explains its apparent asymmetry: lack of height and large base. The restoration of the burial monument started in May 2007, it was carried out by first fulfilling a series of non-invasive analyses using a transportable EDXRF to map the composition of the alloy and evaluate the diagnostic capabilities for deterioration processes of the bronze surface. As a consequence of the first non-invasive diagnostic campaign, a second campaign of micro invasive tests was planned and carried out. The samples were analysed with SEM-EDS and XRF techniques. In this article some of the results of the EDXRF tests will be shown together with the procedures set up to maximize the diagnostic information obtained and minimize the need of microsampling from the artefact. The results and the statistical analysis of data show that a straightforward planning of the measurements can give several, sometimes unexpected, results in the definition of the state of conservation of the monument and also from an archaeometric point of view. With a high amount of data, the use of statistical analysis is necessary, for example in our case, the analysis of the variance confirmed the hypothesis of the use of different alloys for the elements of the panels.