Studies of melanocyte and melanoma biology using monocultures of cells are limited because of culture-induced morphology changes and expression of genes related to growth, migration, and invasion, which do not reflect the in situ phenotype of normal melanocytes, nevus cells, or melanoma cells from biologically early progression stages. The development of organotypic cultures of human skin, in which culture artifacts are greatly diminished and cell-matrix and cell-cell interactions between different cell types can be investigated in a three-dimensional system, has opened a new era for melanoma research. Long-term in vivo studies, especially important for melanomagenesis and melanoma metastasis have become possible through grafting of skin reconstructs to immunodeficient laboratory animals. In this review, principles and different methods of skin reconstruction are introduced with focus on the application for pigment cell biology.