p73, a first p53 relative, has recently been identified and demonstrated to be monoallelically expressed. This protein shows significant amino acid sequence and functional similarities to p53. However, it is unclear whether this protein functions as a tumor suppressor. To elucidate the role of p73 in tumor development, we investigated the expression of the p73 gene in lung cancer. In a comparison between normal lung and tumor tissues, p73 was more highly expressed in tumors. Moreover, using a C/T polymorphism in exon 2 for allele-specific expression analysis in 21 pairs of lung tumors and matched normal tissues, we found that five heterozygous samples exclusively expressed both alleles in tumors while showing monoallelic expression in matched normal tissues. This result was confirmed by single-nucleotide primer extension analysis. Mutation analysis of all 13 coding exons of the gene in 21 lung tumor DNAs revealed several polymorphisms, but no tumor-specific mutations were detected. These findings strongly suggest that p73 may play an important role in lung tumorigenesis through activation of a silent allele and overexpression of wild-type p73 rather than as a tumor suppressor.