The p63 protein, a member of the p53 family of nuclear transcription factors, is characterized by different capabilities of transactivating reporter genes, inducing apoptosis, and functioning as dominant‐negative agent. This study evaluated the prevalence and prognostic implications of p63 immunoreactivity in 221 patients with stage I non‐small cell lung carcinoma (NSCLC) and in 57 patients with stage I–IV neuroendocrine tumours (NET). The results were correlated with the tumour proliferative fraction, the accumulation of p53 protein, and with patient survival. p63 immunoreactivity was seen in 109/118 squamous cell carcinomas, 15/95 adenocarcinomas, 2/2 adenosquamous carcinomas, 4/6 large cell carcinomas, 9/20 poorly differentiated NET, and 1/37 typical and atypical carcinoids (p < 0.001). Furthermore, the prevalence of p63‐immunoreactive cells increased progressively from pre‐neoplastic and pre‐invasive lesions to invasive squamous cell carcinomas. In these latter tumours, but not in adenocarcinomas, p63 immunoreactivity correlated directly with the tumour proliferative fraction (p = 0.028), and inversely with the tumour grade (p = 0.004). No relationship was found with p53 protein immunoreactivity or the other clinico‐pathological variables examined. Although p63 is likely to be involved in the development of pulmonary squamous cell carcinoma, it does not carry any prognostic implication for NSCLC patients. Copyright © 2002 John Wiley & Sons, Ltd.