Natural antisense transcripts (NATs) constitute a class of non-coding RNAs that have emerged as important regulators of gene expression in an epigenetic manner. Tumor suppressor P53 plays an important role in the cell-intrinsic responses to genome instability, including a transient cell cycle arrest, senescence and apoptosis. A Wrap53α (WD40-encoding RNA anti-sense to p53) that transcription initiated from exon 1α is required for p53 induction upon DNA damage. However, involvement of Wrap53α in lung cancer has not been reported to date. We determined the methylation status of Wrap53α genes in primary lung tissues using a methylation-specific PCR (MSP) and evaluated their relationship with clinicopatholgial features and sur-vival in patients with non-small cell lung cancer (NSCLC). Wrap53α promoter was unmethylated in most malignant and corre-sponding nonmalignant tissues. Wrap53α methylation was detected in 19 (13.3%) of 146 tumor tissues and 12 (8.2%) of 146 normal tissues. In addition, Wrap53α methylation in normal and non-malignant tissues was frequently detected in p53 muta-tion-negative patients and in patients with stages II-IV. Patients with Wrap53α methylation in normal tissues exhibited sig-nificantly worse overall survival, while methylation in tumor tissues did not affect the survival outcome of patients. These findings suggest that Wrap53α methylation play a role in lung carcinogenesis. However, further studies with a large number of cases are needed to confirm this.