In the last decades, the very fast improvement of the analytical instrumentation has led to the possibility of quickly and easily getting a lot of data; in turn, the need of advanced statistical methods suitable to extract the full information furnished by instruments has increased. Such kind of data treatments is particularly important in any case of continuous monitoring of one or more parameters, so the microclimate monitoring is a typical example for this application. Microclimate control is essential in the conservation of Cultural Heritage (CH), but decisions on optimal conservation parameters cannot base only on existing norms that do not take into account the environment’s history. Often CH has survived for many centuries in conditions that must be considered risky but also a stable state (equilibrium) resulting from a long adaptation process during which a more or less heavy damage occurred to the materials. Any successive change of microclimate parameters has interrupted this equilibrium conditions and has induced further damage to material until a new equilibrium is reached; dimension and frequency of changes are proportional to the expected damage. This thermodynamic consideration provides the background for a CH conservation project based on microclimate control and highlights the importance of environmental monitoring for the identification of equilibrium parameters to be maintained. In 2010, we monitored the microclimate of an important historical building in Rome, the Mamertino Carcer, before its opening to visitors. One year later, we repeated the monitoring in the presence of visitors, and here, we present a careful choice of multivariate data treatments adopted for an enough, simple and immediate evaluation of the microclimatic changes; this allows an easier understanding also for persons with not too deep scientific background, such as Superintendents and, in turn, really useful information to provide suggestions for a conservation project. Results evidenced the expected loss of isolation of the site that occurred by opening to visitors; this led to wider excursions of both temperature and relative humidity and, in turn, to a worsening of the conservative conditions. Surely, a monitoring of particulate matter, correlated to air fluxes and, in turn, to microclimate, is of fundamental importance for the conservation of frescoes and will be object of one of our future diagnostic interventions in the site.