Introduction: One of the aims of the SENTIERI-ReNaM Project is to identify excess risks of malignant mesothelioma in National Priority Contaminated Sites and to discuss the results by means of data on individual case histories available from the Italian National Mesothelioma Register (ReNaM). Methods: Incident cases of mesothelioma and Standardized Incidence Ratios (SIRs), with corresponding 95% confidence intervals, have been estimated in 39 sites for both gender, in the period 2000-2011. Age-standardized rates of Italian geographical macro-areas (North-Eastern, North-Western, Centre, South-Islands) have been used to estimate expected cases. For each analyzed site the occupational and non-occupational asbestos exposure modalities are discussed. Results: An excess of mesothelioma incidence is confirmed in sites with a known past history of direct use of asbestos, such as Balangero (chrysotile mine) for men (SIR=197.11, 95% CI: 82.04-473.56), Casale Monferrato (asbestos-cement plant) for men and women (SIR=910.70, 95% CI: 816.45-1012.84 and SIR=1338.1, 95%CI: 1176.7-1515.4), Broni (asbestos-cement plant) for men and women (SIR=1288.52, 95%CI: 981.86-1690.97 and SIR=2006.7, 95%CI: 1488.3-2705.8), and in coastal areas (shipyards and harbours) (e.g. Trieste, La Spezia, Venice and Leghorn). A significant excess of mesothelioma has been observed in settings without documented direct use of asbestos, such as Cengio and Saliceto in the North, Falconara Marittima in the Centre, and the Litorale Domizio Flegreo and Agro Aversano in Southern Italy. Conclusion: The analysis of occupational risk in geographical studies with an ecological design is essential to attribute a weight to etiological factors. The evaluation of environmental risk for people living in polluted areas, considering also the risk for workers, and the assessment of a risk produced by industrial settlements, are feasible through the use of data available from surveillance systems of occupational tumors.