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Simple Summary: This study recruited 3272 non-small cell lung cancer (NSCLC) cases to analyze the predictive abilities of serum tumor markers (CEA, SCC-Ag, CYFRA 21-1, NSE, ProGRP, TPSA and CA199) for metastasis and clinical stage, and found that tumor marker levels may be indicative of tumor metastasis (intrapulmonary, lymphatic and distant metastasis) and stage. Increased CEA and CA199 provided an accurate prediction of intrapulmonary and distant metastasis. Increased CEA, CYFRA 21-1 and CA199 provided an accurate prediction of lymphatic metastasis and higher tumor stage. Combined detection of serum tumor markers can indicate tumor metastasis and stage in NSCLC patients. Objective: This study aimed to explore the roles of serum tumor markers for metastasis and stage of non-small cell lung cancer (NSCLC). Methods: This study recruited 3272 NSCLC patients admitted to the Tianjin Union Medical Center and the Tianjin Medical University Cancer Institute and Hospital. The predictive abilities of some serum tumor markers (carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), cytokeratin-19 fragment (CYFRA 21-1), neuron-specific enolase (NSE), pro-gastrin-releasing peptide (ProGRP), total prostate-specific antigen (TPSA) and carbohydrate antigen 199 (CA199)) for NSCLC metastasis (intrapulmonary, lymphatic and distant metastasis) and clinical stage were analyzed. Results: Tumor markers exhibited different numerical and proportional distributions in NSCLC patients. Elevated CEA, CYFRA 21-1 and CA199 levels were indicative of tumor metastasis and stage. Increased CEA and CA199 provided an accurate prediction of intrapulmonary and distant metastasis with the area under the receiver operator characteristic curve (AUC) of 0.69 both (p < 0.001); Increased CEA, CYFRA 21-1 and CA199 provided an accurate prediction of lymphatic metastasis with the AUC of 0.62 (p < 0.001). Conclusion: Combined detection of serum tumor markers can indicate tumor metastasis and stage in NSCLC patients. [ABSTRACT FROM AUTHOR]