We examined the expression of angiopoietin-2 in serum samples from patients diagnosed with colorectal cancer and healthy volunteers and investigated the feasibility of using angiopoietin-2 as a potential diagnostic colorectal cancer biomarker. Enzyme-linked immunosorbent assays were used to measure the levels of angiopoietin-2 in patients with colorectal cancer and healthy control subjects. Correlations between serum angiopoietin-2 levels and clinicopathological factors were investigated. A receiver operating characteristic curve was used to predict cut-off values of the markers. Serum concentrations of angiopoietin-2 were significantly higher in patients with colorectal cancer than in controls (2896 ± 1273 vs 1554 ± 991 pg/mL, P = 0.004). Serum angiopoietin-2 expression levels were significantly positively correlated with TNM stage (P = 0.003), lymph node involvement (P = 0.04), and distant metastases (P = 0.005). Receiver operating characteristic curve analysis revealed that serum level of angiopoietin-2 was a potential biomarker for differentiating colorectal cancer patients from controls and had a receiver operating characteristic area under the curve of 0.859 (95% confidence interval = 0.740-0.978). At a cut-off value of 2710 pg/mL, the sensitivity was 79.3% and the specificity was 82.4%. Our results suggest that angiopoietin-2 can be used as a diagnostic biomarker for colorectal cancer in clinical practice. Additional studies are needed to clarify the detailed mechanism of angiopoietin-2 in the carcinogenesis and metastasis of colorectal cancer.