BACKGROUND AND OBJECTIVES After the notification by a general practitioner of a high frequency of soft tissue sarcomas among subjects living close to the industrial area of the city of Mantua (northern Italy), the local Medical Association carried out a formal epidemiologic investigation to corroborate or falsify the hypothesized excess. Several industrial activities of the area were hypothesized to be a source of environmental pollution that might cause soft tissue sarcomas. METHODS All general practitioners working in the area were requested to report the cases of soft tissue sarcoma diagnosed in the study area. Person-years of observation were computed for all subjects who ever resided in the area between 1984 and 1997. Expected incidence was computed from the cancer registry covering a nearby province (Varese) and from the pool of Italian cancer registries. Peripheral soft tissue sarcoma and visceral sarcomas were included in the analysis. RESULTS AND CONCLUSIONS Overall, 20 cases were observed in a 13-year period, 8.87 were expected from the Varese province cancer registry and 7.72 from the pool of Italian registries. The corresponding standardized morbidity ratios were 2.25 (95% confidence interval, 1.34-3.47) and 2.6 (95% confidence interval, 1.6-4.0), respectively. A significant excess persisted after excluding 5 cases that had been the object of the original notification. We hypothesize that the soft tissue sarcoma excess may have resulted from environmental pollution by industrial toxic emissions, which likely included 2,3,7,8-tetrachloro-dibenzo-dioxin.