Abstract Estrogen receptor protein (ERP) concentrations were determined by the sucrose diffusion method in primary tumors and one or more metastases in twenty-nine patients with breast cancer. Concurrence of ERP concentrations between primaries and at least some metastases was found in 76 per cent of cases. Multiple metastases were assayed in ten cases, three of which demonstrated highly variable concentrations. It was concluded that clinically significant differences in ERP concentrations often exist between primary breast cancers and their metastases as well as between different metastases from the same tumor, accounting for the lack of responsiveness of some ERP-“positive” tumors and for mixed responses to hormonal or endocrine therapy. Assay of an isolated metastasis may be no more reliable in predicting overall patient benefit from therapy than assay of the primary itself.