A low incidence of lung carcinoma has been reported in cases of prolonged use of aspirin. Cyclooxygenase (COX) 2 expression is frequently seen in adenocarcinoma of the lung, but COX-2 expression in atypical adenomatous hyperplasia (AAH), a possible precursor lesion of adenocarcinoma of the lung, is not known. COX-2 expression was immunohistochemically evaluated in a cohort of 20 cuboidal cell hyperplasias (CCH), 81 atypical adenomatous hyperplasias (AAH), 18 bronchioloalveolar carcinomas (BAC), and 88 invasive adenocarcinomas (I-Ad). The relationship between COX-2 expression and clinicopathologic factors and survival was examined. COX-2 overexpression was detected in over 80% of CCH, AAH, BAC, and I-Ad. However, overexpression was diffuse in AAH (71.6%) and BAC (66.7%). No relationship was found between COX-2 expression and clinicopathological factors or survival. COX-2 expression was most frequently detected in AAH. These findings, taken with previous reports that treatment with COX-2 inhibitor suppresses human colon carcinogenesis, suggest that inhibition of COX-2 may reduce the incidence of human adenocarcinoma of the lung.