It has been suggested that neuroleptic medication may decrease cancer risk. We compared cancer risks in a population-based cohort study of 25 264 users (≥2 prescriptions) of neuroleptic medications in the county of North Jutland, Denmark, during 1989-2002, with that of county residents who did not receive such prescriptions. Statistical analyses were based on age-standardisation and Poisson regression analysis, adjusting for age, calendar period, COPD, liver cirrhosis or alcoholism, use of NSAID, and, for breast cancer, additionally for use of hormone therapy, age at first birth, and number of children. Use of neuroleptic medications was associated with a decreased risk for rectal cancer in both women and men (adjusted IRRs of 0.61 (95% confidence interval, 0.41-0.91) and 0.82 (0.56-1.19), respectively) and for colon cancer in female users (0.78; 0.62-0.98). Some risk reduction was seen for prostate cancer (0.87; 0.69-1.08), but breast cancer risk was close to unity (0.93; 0.74-1.17). Overall, treatment with neuroleptic medications was not related to a reduced risk of cancer, but for cancers of the rectum, colon and prostate there were suggestive decreases in risk.