OBJECTIVE: To delineate a perceived association of estradiol versus estradiol plus norethisterone hormone therapy on the prevalence of colorectal cancer in postmenopausal women. METHODS: The Women's Health in the Lund Area (WHILA) project covers 10,766 women aged 50-60 years, living in the Lund area, Sweden. Out of this population, 6908 (64%) women completed questionnaires, underwent physical and laboratory assessments and had self-reported information regarding colorectal cancer. Four hundred and twenty-two (6%) were premenopausal (PM), 3600 (52%) were postmenopausal without hormone therapy (PM0), 2452 (36%) were postmenopausal with combined hormone therapy (PMT-HT) and 364 (5%) were postmenopausal with estrogen monotherapy (PMT-E). RESULTS: There were 21 cases of colorectal cancer (0.3%), one in the PM group, 16 in the PM0 group, two in the PMT-HT group and another two in the PMT-E group. Colorectal cancer prevalence was lower in the PMT-HT than in the PM0 group (odds ratio (OR) = 0.18, 95% confidence interval (CI) = 0.04-0.80). However, for the PMT-E group, the OR (95% CI) was 1.02 (0.86-1.20). There was a positive association between low physical activity (p = 0.04), low parity (p = 0.02) and risk of colorectal cancer. CONCLUSION: Combined hormone therapy seemed to be associated with a lower risk of colorectal cancer in postmenopausal women in contrast to estrogen monotherapy. Hence the progestin might have a protective role.