The most common localisation of melanoma is skin, however it may also occur within oral mucosa, eyeball, and brain. Melanoma results from carcinogenic transformation of normal melanocytes and may originate in pigment changes or de novo in normal skin. The occurrence and growth of melanoma are due to both genetic predispositions and environmental factors, especially UV radiation [1, 2]. The process of transformation of melanocytes into dysplastic cells, and further into melanoma cells with radial spread without metastatic tendencies as well as vertical spread with possible metastases, is multistage. It requires changes in: signal transduction patterns, proliferative activity, migration ability, and ability of cancer cells to destroy the extracellular matrix (ECM). Extracellular matrix metalloproteinases are enzymes capable of destruction of three-dimensional ECM structure, therefore enable the migration of cancer cells. The disturbance of the interactions between cells in the primary lesion together with the ability to transform and destroy structural barriers of the ECM as well as intensified mobility of cancer cells determine its further infiltration to the surrounding tissues, carcinogenic cells migration and distant metastases [3]. During the transformation of normal melanocytes into melanoma cells the expression of extracellular matrix metalloproteinases changes between the consecutive stages of cancer development. Vertical growth and the formation of metastases requires strict cooperation between melanoma and normal skin cells since during the first stages of infiltration keratinocytes and fibroblasts produce extracellular matrix metalloproteinases [4, 5, 6]. Their expression may be regulated by the tumour itself due to melanoma cells ability to produce EMMPRIN (extracellular matrix metalloproteinase inducer). This factor stimulates fi broblasts surrounding cancer to synthesise extracellular matrix metalloproteinases [7]. The role of extracellular matrix metalloproteinases in the cancer invasion is determined by some mechanisms infl uencing the expression and activation of these enzymes, substrate specificity of each extracellular matrix metalloproteinase, their influence on cytokine net, growth factors, and mutual interactions between cells and the extracellular matrix surrounding them [3].