Treatment of metastatic breast cancer based on the estrogen receptor content (ER) of the primary tumor builds on the assumption that the ER status of the primary tumor and the metastases are largely equal. Studies addressing this question have used ligand-binding assays for ER determination and have consequently been subject to the limitations of this technique. Reported disparity rates have been 20%. In order to avoid some of these limitations, we used an immunohistochemical assay in paraffin-embedded tissue. Among a total of 92 examined regional lymph node metastases, ER status was equal with that of their 37 primaries in 84 cases (91%). Semiquantified ER content was significantly correlated in primary tumor and the metastases (r = 0.67, p less than 0.001). Among a total of 51 distant metastases, equal ER status was found in 44 (86%) cases and a quantitative relationship could not be established. Disparities can be due to methodological errors in the histochemical assay or tumor heterogeneity.