Epidermal growth factor receptor (EGFr) is expressed in human bronchial epithelial cells, and non-small cell lung cancers express increased EGFr. Squamous metaplasia of the bronchial epithelium occurs in chronic smokers and is considered an early premalignant change. In this study, EGFr expression was examined in biopsies of histologically normal and metaplastic bronchial tissues obtained from 69 smokers who were enrolled in a randomized placebo-controlled chemoprevention trial. This trial tested the effects of 6 months of treatment with 13-cis retinoic acid (13cRA) on bronchial metaplasia. EGFr expression was examined as a marker of bronchial metaplasia and response to 13cRA treatment. In bronchial biopsies obtained from patients in this study, EGFr expression was higher in metaplastic biopsies than in normal biopsies (P = 0.02). Smoking cessation during treatment correlated with reduced metaplasia (P < 0.001) and EGFr expression (P = 0.02), but multivariate analysis suggested that this effect of smoking cessation on EGFr expression was dependent upon reversal of bronchial metaplasia. 13cRA treatment did not alter EGFr expression (P = 0.23). Baseline EGFr expression levels in metaplastic biopsies did not predict metaplasia reversal. This study demonstrated that increased EGFr expression is a biomarker of bronchial metaplasia, but it did not support the hypothesis that EGFr is a biomarker of retinoid response in lung cancer chemoprevention trials.