The ability of tumor cells to adhere and detach from extra cellular matrix and endothelial cells is a crucial step in the metastatic process and may alter the clinical prognosis of human cutaneous melanoma. This study evaluates the immunohistochemical expression pattern of MMP-9 and CD44 in cutaneous melanocytic lesions. Methods: Forty-three nevomelanocytic lesions (10 ordinary, 6 spitz, 6 dysplastic, 6 melanoma in situ and 15 invasive melanoma). Sex normal skin lesions were taken as a control. All lesions were subjected to H&E and immunostaining for MMP-9 and CD44. Results: The results of MMP-9 immunostaining showed positive expression in 66.7 % of melanoma in situ and 80 % of invasive melanoma, while all benign lesions showed negative reactivity. CD44 immunostaining showed 100 % positivity in all benign and in situ melanoma and 66.7 % of invasive melanoma lesions. A significant inverse relation was found between both MMP-9 and CD44 expression and size (Bresslow) and depth (Clark's level) of invasion (0.001). Conclusions: Coexpression of MMP-9 and CD44 immunostain expression are important factors in determining melanoma cell invasion and metastatic formation. MMP-9 was highly predictive of patients at high risk for melanoma progression and invasion.