Glycoprotein nonmetastatic melanoma B (GPNMB) is a type I transmembrane glycoprotein which is overexpressed in many tumors and seems to play a critical role in metastasis of malignant tumors. The purpose of this study was to determine GPNMB expression in small cell lung cancer (SCLC) and analyze the prognostic value in patients with SCLC. A total of 132 cases of SCLCs were analyzed immunohistochemically on tissue microarrays (TMAs). Patients were divided into weak-positive and strong-positive GPNMB groups. In addition, serum GPNMB was evaluated by enzyme-linked immunosorbent assay (ELISA). The average serum GPNMB concentration was 1054.15 ± 363.71 pg/mL in the weak-positive group, 2611.52 ± 457.57 pg/mL in the strong-positive group, and 427.61 ± 273.9 pg/mL in the control. The strong-positive group showed significantly higher serum GPNMB levels than the weak-positive group and healthy control (p < 0.01). Overall survival in the weak-positive GPNMB group was significantly longer than in the strong-positive group (27 months vs 15 months, p < 0.01). These results suggest that the expression of GPNMB may be useful as a prognostic indicator in patients with SCLC.