The disruption of p16/pRb pathway has been reported in several types of human cancer including lung cancer. However, the etiological and prognostic involvement of this pathway remains poorly defined in lung tumorigenesis in Taiwan. Therefore, we investigated the expressions of p16 and pRb in 107 non-small cell lung cancer (NSCLC) patients by immunohistochemical analysis. The associations of altered p16 and pRb expressions with prognosis were also examined. Sixty-four specimens (59.8%) exhibited alteration of p16 and/or pRb expression, with 49.5 and 22.4% of the tumors failing to express p16 and pRb, respectively. However, there was no reciprocally correlated expression of p16 and pRb. Negative p16 and pRb expression did not correlate well with patients' clinicopathological parameters such as age, sex, smoking habit, tumor type, and tumor stage. In addition, negative p16 and pRb expression was not statistically associated with poor prognosis (P=0.10 and P=0.74, respectively). Our results suggested that the disruption of the p16/pRb pathway plays a significant role in NSCLC tumorigenesis whereas it may not have significant importance in the prognostic evaluation of NSCLC in Taiwan.