Gene methylation and K-ras mutations were examined in tumor and paired serum DNA of 50 resected non-small-cell lung cancer patients. RASSF1A, death associated protein kinase and target of methylation-induced silencing were methylated in 17/50 (34%), 23/50 (45%) and 18/50 (35%) tumors, respectively, and in 17/50 (34%), 20/50 (40%) and 17/50 (34%) sera, respectively. Methylation in tumor and serum were closely correlated (P=0.001), but no correlation was found with survival. Twelve K-ras mutations (cysteine) were found in serum and nine mutations were found in tumor (five cysteine, one alanine, one aspartic, one arginine, and one valine). K-ras mutations in serum correlated significantly with survival (P=0.01).