MelanomaMelanoma is a skin cancerSkin cancer that originates from melanocytes, cells that sit in the basal layer of the epidermis and synthesize melanin. The gold standard for the diagnosisDiagnosis is histopathologic evaluation; however, melanoma can show a wide range of histopathologic features, including subtle histologic atypia, which can pose diagnostic challenges. Additionally, there are other melanocytic tumors that remain incompletely understood, designated as melanocytic tumors of uncertain malignant potential (MELTUMP). Biomarkers could potentially address limitations in disease screening, diagnosis, prognosis, and management of melanoma. This chapter focuses on analyzing the biomarkersBiomarkers most closely associated with clinical outcomes in melanoma patients. We conducted a literature review of 14 biomarkers and used classification standards provided by the World Health Organization (WHO). In this review, we discuss the measurable levels of antigens, proteins, and antibodies associated with melanomaMelanoma diagnosis, prognosis, and response to treatmentTreatment. The presence and extent of immunohistochemical staining, the serum levels of biomarkers, and the presence of inflammatory cellInflammatory cells infiltrates can be analyzed to identify patients who qualify for further testing for melanoma, to distinguish malignant melanomaMelanoma from benign nevi, to differentiate melanoma from other tumor types, to predict patient outcomes, to monitor the progression of melanoma, and to predict response to therapies.