Objective. Elevated serum Mac 2-binding protein (M2BP) levels have been observed in some cancers. As far as we know, its importance has not been investigated in esophageal squamous cell carcinoma (ESCC). The investigated problem of this study was to evaluate whether there was a difference between ESCC patients and the control group in terms of M2BP. Also, we evaluated the diagnostic performance of serum M2BP alone or in combination with the CEA for patients with ESCC. Material and Methods. Blood serum samples were collected from 50 healthy donors and 150 patients with ESCC. M2BP levels of all 200 samples were quantified by ELISA (enzyme-linked immunosorbent assay). Patients who had been diagnosed with ESCC and did not have any other malignancies were enrolled to study. Results. The two groups did not significantly differ in terms of age (p > 0 05). In the control group, the mean serum M2BP level was 14.97 coproduct 3.46 ng/mL. The mean serum M2BP level of the ESCC patients was 176.65 +/- 22.14 ng/mL. The serum M2BP level was significantly higher in patients with ESCC than in the control group (p < 0 001). Gender was also comparable in both groups (p = 0 695). Conclusions. Our analysis demonstrated that this marker may be associated with the mechanism of the disease. Despite that serum M2BP is not a specific marker for ESCC, it can be used as an adjuvant biomarker for the diagnosis of ESCC.