Skin tumorigenesis is linked to inflammatory chemokines accumulation that can induce cancer-associated immune-suppression. Deregulation of the CXCR4/CXCL12 axis was reported in melanoma tumorigenesis while also linked to BRAF mutation. Some chemokine-receptor patterns can direct the organ-specific metastasis. CXCL10 can help to prognosticate high-risk patients as it is a chemokine that differentiated patients with vs. metastasis free ones. Besides serum/plasma, chemokine identification in the cerebrospinal fluid of melanoma patients can indicate brain metastasis. Interplay between suppressed and elevated chemokines in cerebrospinal fluid can pinpoint an aggressive melanoma brain metastasis. Chemokines are gaining rapid momentum in the biomarker discovery domain aiding melanoma prognosis and high-risk patients' stratification.