Risk factors for breast carcinoma in situ and invasive breast cancer were compared using data from 61,844 women (61% post-menopausal) with no prior breast cancer and at least one screening mammogram between April 1, 1996 and June 30, 2001. The women were followed until a subsequent mammogram before July 1, 2001, or a benign biopsy or breast cancer diagnosis before June 30, 2002. A total of 1,191 breast cancers (300 in situ and 891 invasive) were diagnosed during an average follow-up of 3.1 years. Multivariate Cox regression models were used to estimate the relative risks (RR) of in situ and invasive cancer associated with family history of breast cancer, age at first childbirth or nulliparity, post-menopausal hormone use, body mass index (BMI), and mammographic breast density. Separate analyses were done for pre- and post-menopausal women. BMI was unrelated to risk of in situ cancer regardless of menopausal status, but was associated with an increased risk of invasive cancer in post-menopausal women (RR = 1.9 for BMI > or = 30 vs. BMI < 22, 95% confidence interval 1.4-2.5). Later childbearing and nulliparity were more strongly associated with in situ than invasive cancer in pre-menopausal women. Post-menopausal hormone use was more strongly associated with invasive disease. RR associated with family history and breast density were similar for in situ cancer and invasive cancer. Results indicating that BMI is related to post-menopausal invasive cancers but unrelated to in situ cancers are consistent with the hypothesis that concomitants of obesity activate proliferation.