While resistance to chemotherapy is a major problem in lung cancer treatment, there is no useful predictor of treatment response. We thus designed this study to determine the utility of p53 and P-glycoprotein expression in predicting the response to chemotherapy in patients with primary lung cancer, retrospectively. We evaluated transbronchial biopsy (TBB) specimens from 60 patients with lung cancer, who were previously untreated. Formalin-fixed, paraffin-embedded TBB specimens were immunostained using anti-p53 antibody (DO-1) and anti-P-glycoprotein antibody (JSB-1). The positivity of p53 was 63%, and that of P-glycoprotein was 17%. No correlation was observed between p53 and P-glycoprotein immunostaining. Positivity of p53 correlated significantly (P = 0.004) with a lack of response to chemotherapy in non-small cell lung cancer (NSCLC), but not in small cell lung cancer (SCLC). In contrast, positivity of P-glycoprotein was correlated with chemotherapy resistance in SCLC (P = 0.003), but not in NSCLC. Multiple logistic regression analysis revealed that positive immunostaining for p53 was a significant risk factor for chemotherapy resistance in NSCLC. These results suggest that immunostaining of p53 and P-glycoprotein for TBB specimens may help to predict response to chemotherapy in NSCLC and SCLC, although the results should be confirmed in a larger, more homogeneous series.