BACKGROUND This study focused on the association between preoperative serum carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (Cyfra 21-1) levels and pathologic parameters in patients with resected non-small-cell lung cancer (NSCLC). METHODS The records of 527 patients who underwent pulmonary resection of NSCLC were reviewed. The association between preoperative serum CEA and Cyfra 21-1 levels and variables that had p-values of less than 0.05 in a t-test or one-way analyses of variance was analyzed by multiple linear regression. RESULTS The mean serum CEA and Cyfra 21-1 levels prior to surgery were 6.8±23.1 mg/dL (range, 0.01 to 390.8 mg/dL) and 5.4±12.3 mg/dL (range, 0.65 to 140.2 mg/dL). The serum CEA levels were associated with tumor (T) and lymph node (N) stage and histology. The serum Cyfra 21-1 levels were associated with T stage, tumor size, and histology. Multiple linear regression indicated that serum CEA levels were associated with T (T3/4 vs. T1: β=8.463, p=0.010) and N stage (N2/3 vs. N0: β=9.208, p<0.001) and histology (adenocarcinoma vs. squamous cell: β=6.838, p=0.001), and serum Cyfra 21-1 levels were associated with tumor size (β=2.579, p<0.001) and histology (squamous cell vs. adenocarcinoma: β=4.420, p=0.020). CONCLUSIONS Serum CEA level was correlated with T and N stage, and Cyfra 21-1 with tumor size. CEA and Cyfra 21-1 showed histologic correlation. CEA is mainly elevated in adenocarcinoma and Cyfra 21-1 in squamous cell carcinoma. These results might be helpful for predicting pathologic status in preoperative NSCLC.