Background: Firm scientific evidence supports the causal association between malignant mesothelioma (MM) and occupational exposure to asbestos. Risk attributable to occupation varies from 30 to 80% across different populations. The existence of a threshold level below which there is no risk of MM is still debated. A prompt and thorough assessment of exposure is essential to evaluate and manage MM cases, from diagnostic and epidemiological points of view. Objectives and methods: To highlight the multiple areas of intervention by Occupational Physicians (OP) in MM evaluation and management, to describe an experience of OP in the province of Brescia. Results: The main areas of interest of the OP are exposure assessment, diagnosis (clinical, etiological), medico-legal issues, social consequences, preventive strategies, risk communication, scientific dispute/uncertainties. By means of an active search, the Brescia MM registry, managed by OP belonging to the local health authority observed 309 MM from 1977 to 2003; the local Institute of Occupational Health, hosted in a hospital of national relevance, evaluated about 200 MM in the last decade. The main outcomes of OP activity are the high percentage of direct interviews, individual case management, expert exposure assessment, etiological diagnosis, counselling, medico-legal assistance, better knowledge of occupational risks, enhanced cooperation among health professionals (oncologists, pathologists, surgeons, pneumologists, general practitioners and OP), important contribution to Registries and to epidemiology (estimates of attributable risks, incidence, survival rates), with positive social and scientific consequences (insurance agencies, trade union organizations, public events, teaching opportunities). Conclusions: This experience highlights the multifaceted role of OP in active research and evaluation of MM cases, in the context of a multidisciplinary approach.