As the prognostic significance of the three most frequently amplified oncogenes in breast cancer (c-myc, int-2/FGF3, and c-erbB-2/neu) is still unclear, and as the amplification of these genes appears to be mutually exclusive, we investigated the prognostic significance of oncogene amplification per se by multivariate analysis in a group of 112 primary human breast cancer cases. Amplification of at least one gene (c-myc, int-2/FGF3, or c-erbB-2/neu), progesterone receptor status, and pathological tumor size were the only independent variables predictive of metastasis-free survival. Moreover, we constructed prognostic profiles by computing risks associated with the three parameters predictive of poor survival and discriminated high-, moderate-, and low-risk categories.