BACKGROUND Organochlorine (OC) pesticides are a group of environmental endocrine disruptors that may be associated with an increased risk for hormone-related cancers including cancers of the breast and prostate. However, epidemiologic evidence is limited and inconsistent. OBJECTIVE We used 1999-2004 National Health and Nutrition Examination Survey data to examine associations between serum concentrations of OC pesticides and prostate and breast cancers. RESULTS After adjustment for other covariates, serum concentrations of beta-hexachlorocyclohexane (HCH) (p for trend = 0.02), trans-nonachlor (p for trend = 0.002), and dieldrin (p for trend = 0.04) were significantly associated with the risk of prevalent prostate cancer. Adjusted odds ratios for the second and third tertiles of detectable values were 1.46 [95% confidence interval (CI), 0.52-4.13] and 3.36 (95% CI, 1.24-9.10) for beta-HCH; 5.84 (95% CI, 1.06-32.2) and 14.1 (95% CI, 2.55-77.9) for trans-nonachlor; and 1.06 (95% CI, 0.30-3.73) and 2.74 (95% CI, 1.01-7.49) for dieldrin compared with concentrations in the lowest tertile or below the limit of detection. However, there was no positive association between serum concentrations of OC pesticides and breast cancer prevalence. CONCLUSIONS Although further study is necessary to confirm these findings, these results suggest that OC pesticide exposures may have a significant effect on cancer risk. Efforts to reduce worldwide OC use are warranted.