A case-study regarding the results of the SENTIERI project on the Brescia-Caffaro NPCS (National Priority Contaminated Site) is reported. This area has been polluted mainly by polychlorinated biphenyls (PCBs), which have been classified recently by the International Agency for Research on Cancer as human carcinogens (group 1), with sufficient evidence for melanoma and limited for non-Hodgkin lymphoma (NHL) and breast cancer. The 3rd report of the SENTIERI project (2014) has shown an excess of cancer incidence with respect to the expected, on the basis of the incidence rates from the pool of Centre-North Italy cancer registries, but a mortality similar to that expected according to the regional rates, for melanoma, NHL and breast cancer. Furthermore, a higher than expected incidence has been found for various cancers which are not associated a priori with PCB exposure. The Brescia Local Health Authority has also carried out an analysis of cancer incidence, which has shown an incidence in the area similar to other ones in North Italy and a cluster of cases centered on Brescia town for melanoma only. A possible explanation of these discrepancies is the use of different reference populations for the comparisons (Region and pool of Centre-North Italy cancer registries), besides possible confounding bias. We discuss here the most critical aspects of modern ecological studies, their potential information content and interpretation limits.