Chemokines are key players in cancer progression as they influence stromal cell composition, tumor vascularization or metastatic trafficking. Investigating the chemokine profile of cutaneous primary melanomas and benign nevi revealed increased expression of CXCL5 in thick compared to thin melanomas and nevi. The expression of CXCL5 positively correlated with the number of attracted neutrophils in primary melanomas. In order to examine the impact of CXCL5 and neutrophils in the disease progression of melanoma we first established a murine xenograft transplantation model using two CXCL5 overexpressing human melanoma cell lines (A375 and M24met). CXCL5 expressing primary xenografts showed increased lymphangiogenesis compared to controls, which correlated with elevated frequencies of lymph node metastasis. We then investigated the differences in neutrophil phenotypes and their engagement with cytotoxic T cells in a syngeneic transplantation model using two CXCL5 overexpressing murine melanoma cell lines (B16F1 and HCmel12). Surprisingly, in this model, we did not detect any CXCL5 dependent differences in vascularization, but identified a microenvironment dependent control of neutrophil phenotype and function. Regardless of the expression of CXCL5, primary melanomas induced protumoral neutrophils, which have the ability to suppress cytotoxic T cells. Contrary, in preferred metastatic sites such as the lungs, resident neutrophils exhibited an antitumoral phenotype with increased ROS production upon CXCL5 stimulation. This lead to reduced frequencies of lung metastasis in the CXCL5 group. Systemic neutrophil depletion reversed this effect. Strongly dependent on the local milieu, neutrophils can act in a protumoral or antitumoral way. Influencing this phenotype switch opens up new therapeutic possibilities.