Stanniocalcin 2 (STC2) is a glycoprotein hormone that plays an important role in calcium and phosphate homeostasis. Furthermore, recent studies have demonstrated that STC2 expression in the primary site is correlated with tumor progression in several types of malignancies. However, few reports have investigated the clinical significance of STC2 expression in the blood of patients with gastric cancer. Therefore, we examined STC2 expression as a molecular blood marker for detection of circulating tumor cells (CTCs) and assessed the relationship between STC2 expression and clinico-pathological features including prognosis in patients with gastric cancer. Quantitative PCR assay was used to assess STC2 mRNA expression in 4 gastric cancer cell lines and in blood specimens from 93 patients with gastric cancer and 22 healthy volunteers. The numbers of STC2 mRNA copies were significantly higher in the gastric cancer cell lines and in blood from patients with gastric cancer than in blood from healthy volunteers (P=0.0002 and P=0.01, respectively). STC2 expression was positive in 43 (46.2%) of the 93 patients with gastric cancer, and its expression was significantly correlated with age, depth of tumor invasion, lymph node metastasis, stage and venous invasion (P=0.023, P=0.045, P=0.035, P=0.007 and P=0.027, respectively). The 5-year survival rate was significantly lower in patients with STC2 expression compared to patients without STC2 expression (P=0.014). Our results indicate that STC2 could be a useful molecular blood marker for predicting tumor progression by monitoring CTCs in patients with gastric cancer.