The p63 genomic sequence was amplified in 88% of squamous cell carcinomas, in 42% of large cell carcinomas, and in 11% of adenocarcinomas of the lung. The predominant splice variant of p63 expressed was DNp63a. Western blot analyses revealed DNp63a expression in the normal bronchus and squamous carcinomas, but not in the normal lung or in adenocarcinomas. Furthermore, p63 genomic amplification and protein staining intensity was associated with better survival. We found a significant increase in the CNs in preinvasive lesions that were graded as being severe dysplasia or higher.