This study addresses the relationship between female sex hormones, obesity, body fat distribution, and breast cancer. Increasing obesity correlated with a progressive fall in sex hormone-binding globulin (SHBG) level and an increase in testosterone level. Premenopausal breast cancer patients were found to have significantly lower levels of SHBG compared with age-matched and weight-matched controls. This difference in SHBG level was not noted in postmenopausal breast cancer patients. The SHBG level decreased with increasing upper body fat localization in breast cancer patients and controls. This effect was more marked in breast cancer patients which may explain our earlier finding that women with upper body fat localization are at increased risk for developing breast cancer.