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In 1976, an accident in a plant near Seveso, Italy, exposed the local population to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Persons residing in three zones of decreasing TCDD contamination (A, B, and R) and a reference population were followed up for cancer occurrence in 1977–1986. The most exposed subgroup (A) was small, and only 14 cancer cases were observed. In zone B, hepatobiliary cancer was elevated, especially for those living in the area for >5 years [relative risk (RR) = 2.8; 95 confidence interval (CI) = 1.2–6.31. Men exhibited an increase in hematologic neoplasms, most notably lymphoreticulosarcoma (RR = 5.7; 95 CI = 1.7–19.0). Women experienced an increased incidence of multiple myeloma (RR = 5.3; 95 CI = 1.2–22.6) and myeloid leukemia (RR = 3.7; 95 CI = 0.9–15.7). In zone R, the incidence of soft tissue tumors and non-Hodgkin's lymphomas was elevated, particularly among persons living in the area for >5 years (RR = 3.5; 95 CI = 1.2–10.4 for sarcomas, and RR = 2.0; 95 CI = 1.2–3.6 for non-Hodgkin's lymphomas). Breast cancer among females was below expectations in the most contaminated zones, and a clear deficit for endometrial cancer was observed in zones B and R. (Epidemiology 1993;4:398–406)