Populations resident in the historical town of Venice and in the inland industrial city of Mestre are at different risk of exposure to environmental pollutants. This case-control study compares the risk of developing lung cancer in the two populations in relation to known risk factors for this neoplasm. A retrospective study of 305 incident cases of lung and 447 frequency-matched population controls was conducted through a standard questionnaire on main risk factors for lung cancer. Completeness of cases was checked against the Venetian Cancer Registry files. The results indicate that lung cancer risk associated with tobacco smoking was high in both areas, although more elevated in Venice islands among heavy smokers. An elevation of risk was associated with housing without a heating system, possibly suggesting a role of worse hygienic conditions. An increased risk associated with exposure to occupational carcinogens was detected in the inland area. In conclusion, lung cancer risk due to tobacco smoking largely affects both the populations, while other risks such as occupation or housing conditions appear to be more population-specific.