Background Glycoprotein non-metastatic melanoma protein B (GPNMB) plays an important role in the pathogenesis of inflammatory and malignant diseases.We investigated the expression of GPNMB in benign and malignant skin diseases.Methods Tissue microarray was performed in the skin tissues of 102 cases including malignant melanoma (MM),squamous cell carcinoma (SCC),basal cell carcinoma (BCC),and benign dermatosis.The expression of GPNMB in the tissues was detected by immunohistochemistry.Twenty cases of normal skin and adjacent neoplastic normal skin tissues were selected as controls.Results GPNMB was positively stained in skin malignancies (38/50,76％),which was significantly higher than that in the control and the benign skin tissues (P=0.001 and ＜0.001 respectively).GPNMB was positively stained in MM (13/15,87％) and SCC (16/20,80％) (P ＜0.001).Significant higher expression of GPNMB was observed in patients aged ≥65years than those less than 65 years (n=11 and n=9 respectively,P=0.027).No significant difference of the expression rates was observed between normal control and BCC; however,stronger intensity was detected in the latter.Negative or weak expression was observed in the controls.Conclusion Over-expression of GPNMB correlated strongly and might play an important role in the pathogenesis of MM and SCC.