Thirty-six pathologic and six clinical characteristics observed in 581 patients enrolled in protocol no. 4 of the National Surgical Adjuvant Breast Project were treated by radical mastectomy and were correlated with five-year treatment failure. The cases were initially stratified according to pathologic nodal status, the most important discriminant in breast cancer. The presence of tumor necrosis, poor tumor differentiation (histologic grade 3) and a tumor size > 4 cm were found by multivariate analyses to influence treatment failure in patients without nodal metastases. Prognosis was usually worse in individuals whose tumors exhibited all of these features than in those in whom only one or two could be detected. Although the sample size was small, life-table analysis also disclosed a highly significant relationship between treatment failure and a germinal center predominance pattern in regional nodes in this subset of patients. Except for this latter, these same discriminants were similarly noted to affect treatment failure in those patients with four or more nodal metastases but not those with only 1--3 positive nodes. A possible explanation for this inconsistency among nodal categories is discussed. Nevertheless, it is concluded that these rather easily measured pathologic parameters represent important discriminants for the prognosis and the design of treatment schemes and subsequent protocols for patients with breast cancer, particularly those without regional nodal metastasis. The findings amplify the importance of intrinsic tumor characteristics as well as possibly host factors in accounting for the clinical behavior of patients with breast cancer.