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Skin cutaneous melanoma has high morbidity and mortality. Identification of reliable and quantitative melanoma biomarkers could facilitate an early diagnosis and improve survival and morbidity rates. CD96 has a significant role in adjusting immune function. Although the abnormal expression of CD96 has been reported to participate in carcinogenesis in many human types of cancer, the bioinformatics role of the CD96 in melanoma is unknown. Expression degrees and their underlying functions were first studied by this study. According to TCGA, GTEx, and gene expression profile interaction analysis dataset in this paper, compared with normal skin tissues, CD96 was expressed at higher levels in human cutaneous melanoma skin tissues. Meanwhile, we detected the relative CD96 expression levels by immunohistochemistry. Gene functional enrichment analyses were applied through cBioPortal database analysis. CD96 was clearly upregulated in skin cutaneous melanoma patients and carried out its effects through regulating several signaling pathways, containing the JAK-STAT, PI3K-Akt, and MAPK. Taken together, the analysis results indicated that CD96 could be used as a new clinical bioindicator as well as an underlying medicinal target for cutaneous melanoma. [ABSTRACT FROM AUTHOR]