AbstractEstrogen receptor mRNA was detected by a non‐radioactive in situ hybridization assay in tumor and non‐neoplastic liver tissues. A synthetic oligo‐nucleotide complementary to the human estrogen receptor mRNA was 3′‐labeled with digoxigenin‐deoxyuridine triphosphate (dUTP). Hybrids were revealed by an alkaline phosphatase‐conjugated anti‐digoxigenin antibody. Fourteen primary hepatocellular carcinoma tissues (and one meta‐static) were obtained at surgery from 15 patients. The corresponding non‐neoplastic liver tissues were available in 13 cases. The estrogen receptor mRNA was detected in 11 tumorous and 7 non‐tumorous liver specimens. The staining was cytoplasmic and involved the majority of transformed hepatocytes, whereas a less widespread and weaker signal was found in normal hepatocytes. Within non‐neoplastic tissue, bile duct epithelial cells could also be occasionally stained, whereas other cell types, such as vasal endothelial cells, were negative. Appropriate controls established the specificity of the reaction. Detection of the estrogen receptor protein by immu‐nohistochemistry in these same specimens was invariably negative. This in situ hybridization assay can therefore be used as a complementary tool to evaluate the estrogen receptor expression within liver cance