Melanocytic behavior, survival, and proliferation are regulated through a complex system of cell-cell adhesion molecules. Pathologic changes leading to development of malignant melanoma, upset the delicate homeostatic balance between melanocytes and keratinocytes and can lead to altered expression of cell-cell adhesion and cell-cell communication molecules. Malignant transformation of melanocytes frequently coincides with loss of E-cadherin expression. We now show loss of another member of the superfamily of classical cadherins, H-cadherin (CDH13), which may be involved in the development of malignant melanoma. The provided data show that H-cadherin expression is lost in nearly 80% of the analyzed melanoma cell lines. Knockdown of H-cadherin using siRNA increases invasive capacity in melanocytes. Functional assays show that the re-expression of H-cadherin decreases migration and invasion capacity, as well as anchorage-independent growth in comparison to control melanoma cells. Furthermore, melanoma cells, which re-express H-cadherin via stable transfection show a reduction in rate of tumor growth in a nu/nu mouse tumor model in comparison to the parental control transfected cell lines. Our study presents for the first time the down-regulation of H-cadherin in malignant melanomas and its possible functional relevance in maintenance healthy skin architecture.