Central pathology review of ductal carcinoma in situ from 1,456 patients enrolled in National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-24 was performed to determine predictors for ipsilateral breast tumor recurrences and contralateral breast cancers. Findings after a median follow-up time of 10.5 years revealed ductal comedo necrosis, micropapillary histologic tumor type, and multifocality to be independent high risk factors for ipsilateral breast tumor recurrence. Risk increased for slight comedo necrosis vs absent and for moderate to marked comedo necrosis vs slight. The presence of a micropapillary tumor type and gross tumor size (> or = 1.0 cm) were independently found as risk factors for contralateral breast cancers. Although 47% of ipsilateral and 66% of contralateral events were invasive carcinomas, overall mortality was only 2.3%, a conundrum possibly related to the small size of the latter. The similar predictive role of comedo necrosis in this study and that reported previously from NSABP B-17 (total of 2,079 patients) strongly supports its role as a simple high-risk predictor for ipsilateral breast tumor recurrences.