Melanoma, due to its metastatic rate, is among the most aggressive forms of skin cancer. Human formyl peptide receptor (FPR) and its variant FPR-like 1 (FPRL1) have been associated with cell migration and invasiveness in neoplasms. We have studied the in situ expression of these receptors in a large series of melanocytic lesions and correlated the expression with clinicopathological features and prognosis. Tissue microarray blocks of 141 cases including nevi (31 cases), primary (84 cases), and metastatic melanomas (26 cases) were semiquantitatively evaluated by immunohistochemistry for the expression of FPR and FPRL1 proteins. A significant association was observed regarding diagnosis and percentage of cells showing expression of FPR (P = 0.0311) and FPRL1 (P = 0.0053). A gain of FPR immunoreactivity was observed in the lesions having ulceration (P = 0.0194) and Breslow thickness (P = 0.044). Also, high FPRL1 cytoplasmic immunoreactivity was seen in lesions without tumor regression (P = 0.04). In addition, in patients with increased cytoplasmic staining for FPR, the probability of disease-specific survival was significantly lower (log rank test, P = 0.0089). Our findings reveal that FPR and FPRL1 are overexpressed in primary melanoma and correlate with aggressive tumor characteristics, underscoring them as potential therapeutic targets.