Aberrations in the pathway composed of p16, cyclin D1/CDK4,6 and pRb (pRb pathway) which controls the transition from G1 to S phase occur frequently in various types of tumors. In the present study we analyzed immunohistochemically the expression of pRb, p16 and cyclin D1 in 1 12 primary non-small cell lung carcinomas (NSCLC). Loss of expression of pRb and p16 proteins was demonstrated in 15/112 cases and 64/112 cases, respectively. Inverse expression of pRb and p16 proteins was observed in 61 cases and was statistically correlated with advanced stage of the disease (p=0.03). Overexpression of cyclin D1 was detected in 34 cases and was more frequently observed in stage I than in stage III of the disease (p=0.02). Concomitant overexpression of cyclin D1 and lack of p16 was observed in 57% of cyclin D1-positive tumors. In summary, 82 of 112 analyzed cases showed an aberrant expression of at least one of the investigated proteins. These results indicate that although pRb protein expression is altered only in a small percentage of NSCLCs, the pRb pathway is disrupted very frequently in this type of tumor. There were no statistically significant correlations between changes in protein expression and histological type of tumor, gender, smoking habits and occupation of patients.