Human leukocyte antigen G (HLA-G) is a non-classical HLA class I molecule involved in inducing tolerance at the feto-maternal interface and in escape of immune response by tumor cells. The aim of the study is to review the published literature on the expression of HLA-G in malignant melanomas and its clinicopathological and prognostic correlates.A systematic search was carried out in electronic databases. Studies dealing with HLA-G expression in surgically-removed human samples were retrieved and analyzed.Of 1737 retrieved articles, 16 were included. The main themes regarded HLA-G expression in malignant melanocytic lesions, assessed by immunohistochemistry (IHC), soluble or molecular techniques, and its relationship with clinicopathological features, such as tumor thickness and malignant behavior. Overall significant HLA-G expression was found in 460/843 tumors (55%), and specifically in 251/556 melanomas (45%) evaluated with IHC, in 208/250 cases (83%) examined with soluble methods and in 13/23 melanoma lesions (57%) tested with polymerase chain reaction. Despite the correlation with parameters indicating an aggressive behavior, no studies demonstrated any prognostic value of HLA-G expression. Furthermore, uveal melanomas were constantly negative for this biomarker.Overall, published data indicate that while HLA-G is involved in the interactions between melanomas and the immune system, it is unlikely to be the only factor to play such a role, therefore making it difficult to designate it as a prognostically relevant molecule. Evidence further suggests that HLA-G is not implicated in the immunobiology of uveal melanomas.