An Australian study of 513 women evaluated associations between obesity and both benign and malignant breast disease, and in particular investigated the role of female sex hormones. Women who gained more than 10 kg from early womanhood had a two-fold increase in risk of developing breast cancer, whereas lean women had a greater risk of being treated for benign breast disease. Obese women with breast cancer were more likely to have Stage II tumors but there was no significant association between obesity and tumor size or estrogen and progesterone receptor status. Obesity was strongly associated with the proportions of nonprotein-bound and albumin-bound estradiol, and inversely associated with sex hormone binding globulin (SHBG) levels and the proportion of SHBG-bound estradiol. In addition, age at menarche was inversely associated, and age at menopause directly associated with recalled weight at those time periods. These data demonstrate weight gain as a risk factor for breast cancer, and suggest a possible mechanism supporting its development.