Serum Dickkopf-1 (DKK-1) is elevated in many malignancies and is an important indicator of malignant potential. However, its significance in esophageal squamous cell cancer (ESCC) has not yet been clarified. We hypothesized a role for DKK-1 in patients with ESCC. The study consisted of 90 ESCC patients and 85 healthy controls. After diagnosis, the level of DKK-1 was measured in the serum samples by enzyme-linked immunosorbent assay and the levels of DKK-1 were much higher in the ESCC patients than in the healthy control group (p < 0.0001). For serum DKK-1, the sensitivity and specificity of the assay were 70 and 80%, respectively. The preoperative serum DKK-1 level was elevated in the ESCC patients. Although serum DKK-1 is not a specific biomarker for ESCC, it might be a useful marker for the diagnosis and treatment of ESCC.