Although c-erbB-2 expression is, in general terms, an ominous prognostic indicator in breast carcinomas, there are suggestions that lack of this oncogene, when combined with analogous lack of estrogen (ER negative) and progesterone receptors (PgR negative)-"triple-negative phenotype", is linked with an equally poor prognosis. We investigated this hypothesis in a series of early ductal breast carcinomas. A total of 116 specimens with early breast cancer, defined as tumors of < or =2 cm in size and clinically negative axilla, were studied immunohistochemically for ER, PgR, and c-erbB-2 expression. The median follow-up was 131 months (range 62-245 months). ER positive tumors had a favorable clinical course, compared to ER negative neoplasms, but only for the first 10 years of follow-up (P = 0.04). Prognosis was poorer for the PgR negative cases, relative to PgR positive tumors (P = 0.005), but this stood true for the entire investigation period. Triple-negative breast carcinomas had a poor prognosis, while triple-positive tumors had a favorable outcome. However, if triple-positive and triple-negative cases were excluded from the original sample, the remaining c-erbB-2 positive cases were connected with poor prognosis, relative to the remaining c-erbB-2 negative tumors. c-erbB-2 oncogene has a complex biological role in early breast carcinomas for its expression characterizes subgroups of patients with both favorable (triple-positive phenotype) and unfavorable prognosis (c-erb-B2 positive cases after excluding triple-positive and triple-negative tumors)-a phenomenon presumably due to activation of different biological pathways. Elucidation of these pathways may determine subgroups of patients with tumors requiring different targeted agents.