['The inactivation of the tumor suppressor gene p16 by methylation (p16M) has been recognized recently as an important process in the oncogenesis for a variety of carcinomas. There have been few reports of its use in lung cancer. We investigate p16M in patients with non-small cell lung cancer (NSCLC).', 'p16M in tumor, plasma, and pleural lavage fluid from patients with resectable NSCLC were investigated by using methylation-specific polymerase chain reaction.', 'Of the 33 patients studied, 14 (42%) had p16M tumors. There was a significant association between p16M tumors and advanced TNM staging (stage III or IV, P=0.047, Fisher exact test). Circulating p16M was identified in 2 of the 14 patients with p16M tumor and was also associated with advanced TNM staging (P=0.049). The presence of plasma p16M in NSCLC patients and in p16M tumor patients was associated with poor survival and shorter disease-free survival (P=0.0028, P=0.0039, Kaplan-Meier log rank). In addition, p16M was present in three preresectional and four postresectional lavage samples. Preresectional p16M was associated with poor survival and shorter disease-free survival (P=0.0085). p16M tumor involving the visceral pleura was significantly associated with positive p16M postresectional lavage.'] Is tumor p16M a possible marker of advanced stage in non-small cell lung cancer?