We describe a female patient with lung adenocarcinoma whose tumor extract was highly positive for prostate specific antigen (PSA) immunoreactivity. PSA was present in its Mr 33,000 free form. Using reverse transcription-PCR, we were able to amplify a 754-bp fragment that specifically hybridized to a PSA RNA probe on Southern blots. The PCR fragment was sequenced and found to represent PSA cDNA and not human glandular kallikrein cDNA. PSA immunoreactivity in the lung tissue was localized by immunohistochemistry to normal epithelial cells adjacent to the tumor which was completely negative for PSA. Tissue culture experiments suggested that beclomethasone, a glucocorticoid used to treat the patient, was able to up-regulate PSA gene expression. This is the first report that unequivocally demonstrates PSA expression in lung tissue. We speculate that PSA expression was mediated by the exogenously administered steroid beclomethasone.