Although the ligand-binding biochemical assay is currently the standard method for the determination of estrogen receptor, it is not readily reproducible, is often inaccurate, and requiresnot always availablefresh tissue. Immunohistochemical analysis of estrogen receptor in paraffin-embedded tissue has improved to a point where it is worth considering the feasibility of its use as a stand-alone technique. For this reason, we compared the results of the charcoal-dextran estrogen receptor assay with the immunohistochemical assay on routinely fixed, paraffin-embedded tumor samples from 166 patients with breast cancer. The results were analyzed for concordance between methods as well as for their individual predictive value for overall survival. At the statistically determined, prognostically optimal threshold of 20 fmol/mg total protein, the ligand-binding and immunohistochemical assay were in agreement in 156 cases (94%) with only 10 discrepancies. Six biochemically negative cases were positive by the immunohistologic method and were interpreted as true positives. Four of these were oligocellular tumors and stained strongly for estrogen receptor. Four cases were biochemically positive and negative by immunohistochemistry. These were interpreted as false negative by immunohistochemistry although they all were near the threshold of the ligand-binding technique and were highly cellular, suggesting a low level of receptorper cell.Analysis of overall survival for this series revealed that both methods provide statistically significant discrimination between high and low risk groups. These results confirm previous studies suggesting that the immunohistochemical method, when performed in adequately fixed, paraffin-embedded tissue is as or more accurate than the ligand-binding assay.