Melanoma is one of the most aggressive cancers and its high metastatic potential has a large impact on the number of melanoma deaths.The pathological diagnosis is still the gold standard for melanoma and immunohistochemistry plays an important role in discriminating between melanomas.Recently,emerging molecular knowledge may lead to further identification of clinically relevant biomarkers,such as S100B,MIA,TA-90IC,5-S-CD,SPARC,CSPG4,HSP105,IMP3,KIF2A,mi R-221,YKL-40,some cancer stem cells(CD133,Nestin,CD166,CD20,CD271)and some monoclonal antibodies(KBA62,PNL2),for malignant melanoma detection,risk stratification and prediction/prognosis.However,all of the current main markers have some shortcomings.For example,all markers have limitations in sensitivity and specificity,even the first-line marker,S100 protein.So,sometimes,many of the classification criteria that have been proposed show considerable overlap,making it difficult to categorize cases reproducibly,based on histopathological criteria alone.Besides that,the increased expression of some proteins in melanomas suggests that there are abnormal proteins synthesized due to the genetic pathway.Therefore,we expect that there will be more instrumental breakthroughs in the abnormal gene field,especially with respect to gene mutation.Ultimately,novel melanoma biomarkers could be found and gradually become targeted treatment strategies for a poor prognosis in advanced melanoma in the near future. Melanoma is one of the most aggressive cancers and its high metastatic potential has a large impact on the number of melanoma deaths.The pathological diagnosis is still the gold standard for melanoma and immunohistochemistry plays an important role in discriminating between melanomas. may lead to further identification of clinically relevant biomarkers such as S100B, MIA, TA-90IC, 5-S-CD, SPARC, CSPG4, HSP105, IMP3, KIF2A, mi R-221, YKL- 40, CD133, Nestin, CD166, CD20, CD271) and some monoclonal antibodies (KBA62, PNL2), for malignant melanoma detection, risk stratification and prediction / prognosis.However, all of the current main marker have some shortcomings. For example, all marker have limitations in sensitivity and specificity, even the first-line marker, S100 protein. so, many, the many of the classification criteria that have been proposed showdings overlap, making it difficult to categorize cases reproducible, based on histopathological c riteria alone .eses that, the increased expression of some proteins in melanomas suggests that there are abnormal proteins synthesized due to the genetic pathway.Therefore, we expect that there will be more instrumental breakthroughs in the abnormal gene field, especially with respect to gene mutations . Ultimately, novel melanoma biomarkers could be found and gradually became targeted treatment strategies for a poor prognosis in advanced melanoma in the near future.