The relationship between erbB-2 oncoprotein overexpression and hormone receptors in breast cancer is controversial. Of 320 infiltrating carcinomas, 75 (23%) showed membranous positivity for erbB-2 protein using CB-11 antibody, with 31 (9.7%) strongly positive. Estrogen and progesterone receptors, determined by both biochemical and immunohistochemical assays, were negative more often in strongly erbB-2 positive tumors, or were positive at lower amounts, than in 56 tumors devoid of CB-11 staining. Strong erbB-2 positivity also correlated with lower patient age, higher histopathologic tumor grade, and higher S phase fraction, but not with tumor size, lymph node involvement, or DNA aneuploidy. Thirty-three lobular carcinomas showed strong erbB-2 positivity as frequently as the overall group (9.1%). Cytoplasmic CB-11 positivity without membrane positivity, thought not to correlate with true erbB-2 positivity, was observed in 189 (59%) tumors with a slight (1-2 +) reaction in 124 (39%) tumors and a moderate-to-strong (3-4 +) reaction in 65 (20%) tumors. Moderate-to-strong cytoplasmic positivity correlated with higher histopathologic grade and negativity for immunohistochemical, but not biochemical, hormone receptors. CB-11 cytoplasmic positivity may have biological significance.