Craniopharyngiomas are histologically benign epithelial neoplasms of the sellar region that frequently exhibit invasive and aggressive local growth. In this study, we have investigated the presence and cellular distribution of estrogen receptor messenger ribonucleic acid by in situ hybridization in 23 surgically removed craniopharyngiomas. All craniopharyngiomas studied, including 19 adamantinomatous and 4 papillary variants, uniformly expressed the estrogen receptor gene. In all cases, an intense estrogen receptor messenger ribonucleic acid hybridization signal was demonstrated; one localized exclusively to the epithelial cells of the tumor. Connective tissue and vascular elements were devoid of hybridization signal. Coexpression of the estrogen receptor protein was also studied by immunohistochemistry. Despite the relative abundance of estrogen receptor message in all cases studied, the estrogen receptor protein was focally but conclusively detected in only two tumors. The basis of this discrepancy is unclear. Progesterone receptor protein was also studied in all cases; however, its definitive presence was noted in only one instance and, in that case, in only occasional nuclei. The expression of the estrogen receptor gene by the proliferative epithelial elements of craniopharyngiomas raises the questions of a possible hormonal component to the genesis and/or progression of the craniopharyngiomas and a potential responsiveness to therapeutic hormonal manipulation.