It has been analyzed the frequency of p16 inactivation in 67 blood samples of patients diagnosed with advanced non-small cell lung cancer (NSCLC), to establish the relationship between p16 inactivation and time to progression (TTP) and overall survival (OS), and its relationship with various clinical parameters. This is a retrospective study of 67 patients diagnosed with advanced NSCLC between August 2000 and July 2003 in the Hospital General de Valencia analysing p16 inactivation by assessing in plasma either loss of heterozygosity (LOH) or p16 promoter methylation. The study shows p16 inactivation in 28.3% (either by LOH or by p16 methylation). No significant differences were found between the group with p16 inactivation and the group without p16 inactivation, either in patients' TTP (31 weeks vs. 24 weeks; p=0.7) or in OS (53 weeks vs. 43 weeks; p=0.48). No relationship was found between the state of p16 and the clinical parameters analyzed (stage, ECOG, histology). Despite the fact that p16 is important in NSCLC carcinogenesis, the data obtained in our study do not allow the prognostic impact of this biological marker to be established.