Malathion is the most common organophosphate insecticide applied in the United States, and while some studies suggest that it may be clastogenic, its carcinogenicity has not been demonstrated in rodents. However, malathion has been associated with non-Hodgkin's lymphoma in several epidemiologic studies. The authors investigated associations between malathion exposure and cancer among 19,717 pesticide applicators enrolled in the Agricultural Health Study between 1993 and 1997. Information on lifetime years and days per year of use and intensity of malathion exposure was obtained with self-administered questionnaires prior to the onset of any cancer. The average follow-up time was 7.5 years (1993-2002). Rate ratios and 95% confidence intervals were calculated using Poisson regression, adjusting for potential confounders. Overall, lifetime days of malathion use (top tertile of exposure, >39 days) was not associated with all cancers combined (rate ratio = 0.97, 95% confidence interval: 0.81, 1.15). The risk of non-Hodgkin's lymphoma was not associated with malathion use, although the number of cases was small. The risk of melanoma with more than 39 lifetime exposure-days was 0.39 (95% confidence interval: 0.14, 1.03). In summary, malathion exposure was not clearly associated with cancer at any of the sites examined. Although the rate ratios for melanoma were reduced, small numbers and lack of experimental evidence suggest that the observed reductions may have arisen by chance.