Estrogen receptor (ER) is a useful immunohistochemical marker of breast carcinomas and is commonly used as a means of distinguishing breast carcinomas from adenocarcinomas of other primary sites, including the lung. Previous reports have yielded conflicting data regarding ER immunoreactivity in primary pulmonary adenocarcinomas. In this study the immunohistochemical expression of ER was evaluated in 55 primary lung adenocarcinomas using the 1D5 antibody clone. Immunohistochemistry for thyroid transcription factor-1 (TTF-1), a sensitive and specific marker of pulmonary adenocarcinomas, was also performed. ER expression was observed in 10 (18%) of 55 lung adenocarcinomas. Most of these pulmonary adenocarcinomas showed ER immunoreactivity of weak or moderate intensity (<25% of tumor cell nuclei). However, two cases exhibited strong ER immunoreactivity (51-75% of neoplastic cells). Forty-six (84%) of the 55 lung adenocarcinomas were TTF-1 positive, including all those that expressed ER. These results indicate that a subset of pulmonary adenocarcinomas can exhibit ER immunoreactivity. As such, caution should be exercised in the use of ER immunohistochemistry alone as a means of distinguishing breast carcinomas from lung adenocarcinomas. In the context of an ER-positive lung neoplasm, strong and extensive TTF-1 immunoreactivity can be regarded as strong supportive evidence for a primary bronchogenic adenocarcinoma.