In a case-control study derived from a cohort of 4661 women with a primary carcinoma in situ of the breast, we investigated age at diagnosis, mode of detection, tumor characteristics, and primary therapy, as prognostic factors for developing invasive breast cancer or dying from breast cancer. From all of the women with a primary carcinoma in situ reported to the Swedish Cancer Registry from 1960 through 1992, we selected as cases all of the women with a ductal carcinoma in situ who later died of breast cancer (n = 39) or who developed a subsequent invasive cancer in either breast (n = 118). From this cohort, we also selected controls matched to the cases by year of diagnosis and health care region. We conducted univariate and multivariate analyses to study the association between risk of invasive cancer or death and the different risk factors. Large size, diameter > or = 25 mm [odds ratio (OR), 3.5; 95% confidence interval (CI), 1.1-11.4] and multifocality (OR, 3.9; 95% CI, 1.2-12.7) increased the risk of breast cancer death in univariate analysis. Postoperative radiotherapy (OR, 0.1; 95% CI, 0.0-1.0) and mastectomy (OR, 0.1-95% CI, 0.0-0.5) lowered the risk of an ipsilateral invasive cancer in multivariate analysis. The risk pattern by treatment category differed between those who had an ipsilateral invasive cancer and those who either had a contralateral cancer or died from breast cancer. The driving forces behind local and generalized disease may differ. Because confounding by indication may influence the effects of different treatments, the results should be interpreted with caution.