Under normal conditions, homeostasis determines whether a cell remains quiescent, proliferates, differentiates, or undergoes apoptosis. In this state of homeostasis, keratinocytes control melanocyte growth and behaviour through a complex system of paracrine growth factors and cell–cell adhesion molecules. Alteration of this delicate homeostatic balance and can lead to altered expression of cell–cell adhesion and cell communication molecules and to the development of melanoma. Melanoma cells escape from this control by keratinocytes through three major mechanisms: (1) down‐regulation of receptors important for communication with keratinocytes such as E‐cadherin, P‐cadherin, desmoglein and connexins, which is achieved through growth factors produced by fibroblasts or keratinocytes; (2) up‐regulation of receptors and signalling molecules not found on melanocytes but important for melanoma–melanoma and melanoma–fibroblast interactions such as N‐cadherin, Mel‐CAM, and zonula occludens protein‐1 (ZO‐1); (3) loss of anchorage to the basement membrane because of an altered expression of the extracellular‐matrix binding integrin family. In the current review, we describe the alterations in cell–cell adhesion and communication associated with melanoma development and progression, and discuss how a greater understanding of these processes may aid the future therapy of this disease.