Mutations of p53 tumor suppressor gene have been shown to contribute to tumorigenesis in a variety of human cancers. Normally, p53 protein degrades rapidly and is not detected by immunohistochemical procedure, but mutant p53 and wild-type p53 stabilized by certain viral oncoproteins can accumulate to immunohistochemically demonstrable levels. Conventional pulmonary adenocarcinomas and bronchioalveolar carcinomas, although morphologically similar, exhibit different biological behavior and clinical prognosis. To explore the differences in the expression of p53 protein in these two tumor types, we performed immunohistochemistry on 10 conventional pulmonary adenocarcinomas and 12 bronchioalveolar carcinomas on formalin-fixed and paraffin-embedded material, using the commercially available monoclonal antibody against the mutant p53 protein. Intense nuclear staining was observed in 80% (8/10) of conventional pulmonary adenocarcinomas, whereas all 12 bronchioalveolar carcinomas were negative for p53 protein. These observations indicate that altered p53 protein (probably mutant) is overexpressed in conventional adenocarcinomas and may be involved in its tumorigenesis or progression. On the other hand, the lack of p53 expression in bronchioalveolar carcinomas suggests that an alternative pathway is likely to be responsible for its tumorigenesis. Furthermore, p53 protein immunostaining may be useful as an adjunct in differentiating conventional pulmonary adenocarcinomas from bronchioalveolar carcinomas.