Introduction: Lung cancer is one of the most lethal malignancies; however, no serum marker has been routinely recommended until now.

Methods: This is a prospective case control study including two groups of patients: Group I—patients with advanced lung cancer and Group II—patients with benign lung disease as control. Serum cytokeratin 19 (CK19) fragment levels were measured at baseline by real-time polymerase chain reaction before first-line chemotherapy. The CK19 cut-off taken was 15-cycle threshold. The primary end point was the comparison of high CK19 in cases and controls. The secondary end point was the correlation between high CK19 and progressive disease (PD), progression-free survival, and overall survival (OS) in advanced lung cancer patients.

Results: A total of 30 patients with advanced lung cancer (16 non-small and 14 small cell lung cancer) and 15 patients with benign lung disease were included and followed up during the period from October 2008 to October 2011 with median follow-up of one and half years. High CK19 was found in 90% of lung cancer cases as compared with 7% in controls (p < 0.001). High CK19 was found in all cases showing PD (p = 0.04). One-year OS in high CK was 61% as compared with 33% in normal CK (p = 0.1).

Conclusion: Serum CK19 fragment is a potential diagnostic and prognostic marker for advanced lung cancer.