Cancers are always associated with cell cycle abnormalities. To clarify the cell cycle abnormalities present in lung adenocarcinomas, various cell cycle regulatory proteins of both the pRb and p53 pathways were studied immunohistochemically in 50 cases of stage I adenocarcinoma of the lung. In regard to the pRb pathway, most adenocarcinomas showed frequent expression of both p16 and pRb proteins, and aberrant expression in the pRb pathway was observed in about one-quarter of stage I adenocarcinomas. In regard to the p53 pathway, the frequency of immunohistochemical positivity was 8% for p14ARF, 64% for MDM2, 20% for p53 and 24% for p21. In this pathway, the immunohistochemical profile of p14ARF-negative/MDM2-positive/p53-negative is characteristic of stage I adenocarcinoma of the lung. An inverse relationship was found between MDM2 and p53 protein and was associated with the differentiation status of stage I adenocarcinoma of the lung. Our results suggest that the disruption of the pRb and p53 pathways is frequently observed in the early stages of lung adenocarcinoma and might play an important role in the growth and differentiation of adenocarcinoma of the lung.