Selective expression of certain chemokine receptors by melanoma cells and the presence of their ligands in tissues might govern organ site-specific metastasis. Because the expression profile of chemokine receptors in tissues of melanocytic origin is unknown, we performed a comprehensive study on melanocytic tissue samples investigating the expression of 18 chemokine receptors at the mRNA level by real-time polymerase chain reaction, using a semiquantitative approach, and of 3 chemokine receptors (CXCR6, CCR9, and XCR1) at the protein level. We report on the de novo expression of CXCR6 in primary melanomas and melanoma metastases, but absence in melanoma cell lines and congenital nevi. CXCR4 and CCR1 were the only 2 chemokine receptors that were consistently expressed in melanocytes, melanoma cell lines, primary, and metastatic melanoma; CCR1 expression increased significantly over progression. CCR9 and XCR1 transcripts were found in melanocytic lesions, and expression was confirmed by immunohistochemistry. Transcripts for CCR10 were not found in any of the lesions, but in some melanoma cell lines. Expression of CCR7 was observed in primary melanomas and some metastases. CCR5 was exclusively expressed in primary melanomas and some cutaneous metastases. Results revealed a restricted and differential pattern of chemokine receptor expression in melanoma tissue, which varies substantially from the expression profile of melanoma cell lines and warrants functional studies on some receptors.