Melanoma is known as an aggressive tumor which shows an increasing incidence and poor prognosis in the metastatic phase. Hence, it seems that diagnosis and effective management (including early diagnosis, choosing of the effective therapeutic platform, caring, and training of patients for early detection) are major aspects of melanoma therapy. Early detection of melanoma is a key point for melanoma therapy.There are various diagnosis options such as assessing of biopsy, imaging techniques, and biomarkers (i.e., several proteins, polymorphism, and liquid biopsy). Among the various biomarkers, assessing circulating tumor cells, cell-free DNAs, cell-free RNAs, and microRNAs (miRNAs) have emerged as powerful diagnosis tools for melanoma patients. Deregulations of these molecules are associated with melanoma pathogenesis. After detection of melanoma, choosing of effective therapeutic regimen is a key step for recovery of melanoma patients. Several studies indicated that various therapeutic approaches including surgery, immunotherapy, systematic therapy, radiation therapy and antibodies therapy could be used as potential therapeutic candidates for melanoma therapy. Caring for melanoma patients is one of the important components of melanoma therapy. Caring and training for melanoma patients could contribute to better monitoring of patients in response to various therapeutic options. Here, we summarized various diagnosis approaches such as assessing biopsy, imaging techniques, and utilization of various biomarkers (i.e., proteins, CTCs, cfDNAs, and miRNAs) as a diagnostic biomarker for detection and monitoring patients with melanoma. Moreover, we highlighted various therapeutic options and caring aspects in patients with melanoma.Melanoma is the fifth most common malignancy in men and the sixth in the women (Siegel et al., 2012). The 5-year survival rate is only 15% for remote metastasis, and a very poor cure rate (American Cancer Society, 2012). Owing to the poor prognosis and the lack of effective treatment options for patients with metastases, much attempt has been made to discover the etiology and pathogenesis of melanoma. Both environmental agents and genetic capacity appear to have an important role in malignancy progression (Miller & Mihm, 2006). The associated risk factors of progression into skin cancer are sun exposure (Gilchrest et al., 1999), the existence of atypical nevi (Hayward, 2003;Tucker et al., 2002), skin pigmentation phenotype, and personal and family histories of malignancy (Gandini et al., 2005; J Cell Physiol. 2019;234:3307-3320.wileyonlinelibrary.com/journal/jcp