About 80 % of lung cancers are carcinomas that are classified histologically as non-small-cell lung carcinoma (NSCLC) and targeted chemotherapy of this cancer is currently based on sensitivity of the primary tumor to specific drugs. The purpose of this study was to compare the levels of four serum markers of cancer and the levels of six molecular markers which are possibly associated with drug selection in the primary tumors and metastatic lymph nodes of 39 consecutive NSCLC patients who were admitted to a single institution in China. Serum markers of cancer (neuron-specific enolase, carcinoembryonic antigen (CEA), cancer antigen 125, cytokeratin fragment 21-1) were measured by an automated electrochemiluminescence system and molecular markers (multidrug resistance protein 1, LDL receptor-related protein, ribonucleotide reductase M1, epidermal growth factor receptor, excision repair cross-complementing gene 1, and breast cancer 1) were measured by immunohistochemistry of the primary tumors and metastatic lymph nodes. The results indicate that the serum level of CEA was higher in NSCLC patients with adenocarcinoma relative to those with squamous cell carcinoma, but no significant differences in the other serum markers. Expression of excision repair cross-complementing gene 1 was significantly different in the primary tumors and metastatic sites of NSCLC patients with adenocarcinoma, but there were no other significant differences. This study provides an initial step toward the development of individualized chemotherapy of NSCLC based on measurement of molecular markers in the primary tumors and metastatic lymph nodes.