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Cutaneous melanoma is a highly malignant tumor type which is characterized by its tendency to give rise to metastases. Stromal relationships are essential for growth and metastasis of solid tumors. In cutaneous melanoma, microscopic level of invasion (Breslow index), overall architecture of cells (horizontal or vertical growth phase), angiogenesis, vessel invasion are morphological features which may carry prognostic significance. As demonstrated by in vivo studies, stromal reaction in melanoma is mainly characterized by collagen and elastin proteolysis preferentially localized around the tumor at the invasive front along with variable angiogenesis and lymphocyte infiltration. On the basis of recent findings, it becomes increasingly evident that resident stromal cells (fibroblasts, endothelial cells) are implicated in the metastatic process, including proliferation, matrix degradation, or migration of melanoma cells through cell-cell cross-talk by soluble factors (proteases, cytokines, growth factors) or by direct contact.