PURPOSE: The aim of this study is to determine whether levels of circulating free DNA (cfDNA) increase according to cancer progression, whether they are restored after surgical resection, and to evaluate cfDNA in gastric cancer patients as a useful biomarker. METHODS: A case-control study design was used. Thirty gastric cancer patients and 34 healthy subjects were enrolled from two hospitals in South Korea. The plasma cfDNA of patients with gastric cancer were obtained before surgery and 24 hours after surgery, and then analyzed by a quantitative, real-time polymerase chain reaction. Plasma samples were also obtained from the control group. RESULTS: The mean levels of cfDNA in the healthy control group, patients with early gastric cancer, and with advanced gastric cancer were 79.78 +/- 8.12 ng/mL, 106.88 +/- 12.40 ng/mL, and 120.23 +/- 10.08 ng/mL, respectively (P < 0.01). Sensitivity was 96.67% and specificity was 94.11% when the cutoff value was 90 ng/mL. Variables representing the tumor burden such as tumor size, T stage, TNM stage, and curative resection are also associated with the levels of cfDNA. The levels of cfDNA in the 24-hour-after-surgery group decreased significantly (112.17 +/- 13.42 ng/mL vs. 77.93 +/- 5.94 ng/mL, P < 0.001) compared to the levels of cfDNA in the preoperation group. CONCLUSION: The changes in the levels of cfDNA can act as reliable biomarkers to detect cancer early, to predict tumor burden, estimate curative resection and even prognosis.