Background Angiopoietin-2 (Ang-2) is one of the critical regulators of tumor angiogenesis. Studies have shown a significant correlation of Ang-2 expression to tumor invasion and metastasis in various human cancers, but little is known about the serum Ang-2 (sAng-2) levels in esophageal squamous cell cancer (ESCC) and its precursors. In this study, we aimed to investigate its role in screening for ESCC and its precursors.Methods We carried out a free endoscopic screening in Feicheng City, a high ESCC incidence area in Shandong Province of China. Serum samples were collected as follows: 91 from normal subjects, 44 from patients with esophagitis,85 from patients with hyperplasia, and 13 from patients with early ESCC. In addition, 28 serum samples were obtained from patients with invasive ESCC undergoing surgery in People's Hospital of Feicheng City. All the subjects of the five groups were diagnosed by histopathology. The sAng-2 levels were tested and compared, and the diagnostic power in early or/and invasive ESCC was calculated in terms of sensitivity and other parameters.Results The sAng-2 levels were (22.0±5.5), (21.3±3.2), (20.5±3.3), (24.0±5.0), and (29.8±5.0) U/ml in normal,esophagitis, hyperplasia, early ESCC, and invasive ESCC groups respectively. It was significantly higher in early ESCC than inhyperplasia group (P=0.009). The invasive ESCC group showed the highest Ang-2 level among all groups (all P=0.000). The sensitivities of sAng-2 to early and invasive ESCC were 23.1% and 78.6% respectively.Conclusion sAng-2 level is related to carcinogenesis and progression of ESCC, but it can not be used to screen for early ESCC.