Aberrant glycosylation plays a major role in the progression of melanoma, but little is known about glycosyltransferases. Glycosyltransferase 8 domain containing 1 (GLT8D1) is located in the Golgi apparatus and is related to transferase activity in mammals. However, its role in cancer remains unclear. The aim of this study was to investigate the expression of GLT8D1 in human melanoma and explore the relationship between GLT8D1 expression and the clinicopathological characteristics of melanoma patients via GEO data analysis combined with clinical patient data. The analysis of 45 malignant melanoma samples and 18 benign nevus samples from the GEO database was performed. Moreover, 67 patients with cutaneous melanoma and 38 patients with mucosal melanoma as well as 40 benign nevus samples were collected for our study. Immunohistochemistry analyses were implemented to evaluate GLT8D1 expression at protein level. The GEO data analysis exhibited that the GLT8D1 mRNA expression was upregulated in the melanoma samples compared with the benign nevus samples. Likewise, GLT8D1 protein expression in the cutaneous melanoma and mucosal melanoma samples was significantly higher than that in the benign nevus tissue samples (P = 0.001 and 0.046, respectively). Furthermore, the GLT8D1 protein expression in cutaneous melanoma was higher than that in mucosal melanoma (P = 0.001). The high GLT8D1 protein expression was remarkably correlated with Clark level (P = 0.027), AJCC stage (P = 0.003), ulceration status (P = 0.041), Ki-67 expression (P = 0.030) and especially with histopathological type (P = 0.001). The results of the Kaplan-Meier survival and Cox regression analyses revealed that cutaneous melanoma patients with high GLT8D1 expression (P = 0.036), Clark level (P = 0.018) and advanced AJCC stage (P = 0.003) encountered poor overall survival. Overall survival (P = 0.040) and progression-free survival (P = 0.019) were worse for the patients with high GLT8D1 expression than for the patients with low expression. These data implied that GLT8D1 could be an independent prognostic factor for an unfavorable prognosis in cutaneous malignant melanoma patients and that GLT8D1 overexpression might serve as a novel prognostic biomarker.