Studies regarding cellular interactions between Langerhans cells and other skin cells are somehow hampered by the difficult cultivation of these cells in vitro. Here, we show that the human MUTZ-3 cell line can be differentiated into Langerhans-like cells in the presence of a cytokine cocktail including GM-CSF, TGF-β1 and TNF-α. We used the expression of langerin, CD1a, CCR6 and the intracellular presence of Birbeck granules to identify the differentiated MUTZ-3 cells (MUTZ-3-LCs). The aim of this study was to integrate MUTZ-3-LCs into a three-dimensional full-thickness skin model. On top of fibroblast-containing collagen matrix a mixture of primary human keratinocytes and MUTZ-3-LCs were seeded and cultured for 24 h. Subsequently, the models were lifted up to the air-liquid interface. Histological evaluation featured a fully stratified epidermis with all characteristic epidermal strata. Langerin-positive cells were detected suprabasally within the epidermis indicating that keratinocytes provide environmental conditions for long-time maintenance of MUTZ-3-LCs. These skin models provide a tool to further investigate the interactions between Langerhans-like cells and other skin cells and particularly learn more about the cutaneous immune response.