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Background. Two interphase argyrophilic nucleolar organizer region (AgNOR) counts have been correlated with ploidy and proliferative activity in patients with ductal carcinoma in situ (DCIS) of the breast. The first is the mean number of AgNORs (mAgNOR); it reflects ploidy. The second is the percentage of nuclei with greater than or equal to five AgNORs/nucleus (pAgNOR); it correlates with proliferative activity. DCIS of the breast is a heterogeneous group of lesions that is not associated uniformly with invasive ductal carcinoma. A significant number of patients with DCIS will, however, progress to invasive ductal carcinoma. Factors identifying the invasive potential of DCIS in these patients have not been defined clearly. The authors postulated that pAgNOR in DCIS may predict the invasive potential of these lesions. Methods. The authors studied 86 cases of DCIS of the breast by the AgNOR silver stain using the two above-mentioned counts. Results. There were 54 comedo and 32 noncomedo DCIS cases. Forty-one cases (47%) were associated with invasive ductal carcinoma. Thirty cases of comedo DCIS (55%) showed mAgNOR counts suggestive of aneuploidy 2.4/nucleus), whereas only seven cases of noncomedo DCIS (22%) showed such counts (P = 0.001). Cases associated with invasion had higher incidence of aneuploid mAgNOR counts (P = 0.0003). The pAgNOR counts in comedo DCIS ranged from 1% to 36% (median, 11%), whereas in noncomedo DCIS pAgNOR counts ranged from 0% to 22% (median, 7%) (P = 0.007). The 41 cases associated with invasion had pAgNOR counts ranging from 3% to 36% (median, 12%), whereas those not associated with invasion had pAgNOR counts ranging from 0% to 24% (median, 5%) (P = 0.000001). This difference was irrespective of the type of DCIS or mAgNOR counts. Conclusions. Comedo DCIS of the breast may show a higher incidence of aneuploidy and increased proliferative activity and invasive ductal carcinoma than does noncomedo DCIS. Ploidy and proliferative activity, measured by AgNOR staining in DCIS, may have a significant predictive value in identifying the invasive potential of these lesions. Cancer 1994; 74:1739-45.