Midkine (MK) is one of a family of heparin-binding growth factors, and increased MK expression is reported in various types of human carcinomas. To clarify the association between serum MK (S-MK) concentrations and gastric cancer, we examined S-MK concentrations of gastric cancer patients (n=275) and healthy controls (n=275). S-MK concentrations of all subjects were measured by enzyme-linked immunosorbent assay (elisa). The medians (25th and 75th percentiles) of S-MK were 192 (123 and 314) pg/mL in the cases and 170 (81 and 273) pg/mL in the controls (P <0.01). We also compared S-MK concentrations in each group divided by the progression stage or histological type of cancer. A difference was observed in the median S-MK concentrations between early and advanced cancers [182 (105 and 301) pg/mL vs 203 (139 and 331) pg/mL, P=0.07], but not between intestinal and diffuse type cancers [185 (121 and 306) pg/mL vs 198 (127 and 323) pg/mL, P=0.51]. We found that those progression stages affect S-MK concentration more strongly than the histological types in gastric cancer patients. Because S-MK seems to reflect the progression stage of gastric cancer, it may serve as a useful marker in the clinical follow-up of gastric cancer patients.