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Objectives The Lombardy Mesothelioma Registry (RML) was established in 2000 in the most populated (9 100 000 residents) and industrialised region of Italy. We evaluated the trend of malignant mesothelioma (MM) in 2000-07 and the sources of asbestos exposure collected from the patient/next-of-kin by a standardised questionnaire. Methods We calculated age-standardised rates (standard: Europe) and analysed the number of cases/year using Poisson regression. We evaluated asbestos exposure profile (occupational, non-occupational, unlikely/unknown) using multinomial logistic regression. Results We recorded 2462 verified MM cases (1574 men, 888 women). The age-standardised rates (×100 000/year) were 3.6 (men) and 1.4 (women). In both genders, we found a 3.0% increase of MM cases/year (p=0.001). Interview was obtained in 2333 cases (94.7%) and directly from patients in 1282. Occupational exposure was found for 1124 (71.4%) men and 322 (36.3%) women. Non-occupational asbestos exposure was more frequent among women (No. 118, 13.3%) than in men (No. 51, 3.2%). We did not find evidence of exposure to asbestos in 399 men (25.3%) and 448 women (50.4%). The exposure profile did not vary over years (p=0.49). Direct interviews were more likely to identify asbestos exposure (p Conclusions The MM burden in Lombardy (among the highest in Italy), are increasing. This increase is real and not due to ascertainment bias. Asbestos exposure was mainly occupational and more frequent among men; we found no variation of the exposure profiles over time. This work was supported by Regione Lombardia Conv. 14013/RU01/06/2010