Protein tyrosyl phosphorylation is an essential component in intracellular signalling, with diverse and crucial functions including mediation of cell proliferation, survival, death, differentiation, migration and attachment. It is regulated by the balance between the activities of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases. A number of PTKs are encoded by proto-oncogenes or viral oncogenes, and are thus strongly implicated in cancer. While a role for PTKs in human melanoma is less firmly established, human melanomas or melanoma cells have been reported to contain more tyrosine phosphate than normal melanocytes, and some receptor PTKs (EPH-A2/ECK and EPH-B3) are overexpressed in over 90% of melanoma cell lines. Other specific PTKs are also frequently overexpressed, including KDR and fibroblast growth factor receptor-4 (FGF-R4), while, interestingly, yet others, such as KIT and FES, are consistently downregulated in melanoma cell lines. All of these differentially expressed PTKs are candidates for gene products important in melanoma development. In addition, PTKs expressed in significant amounts in both benign and malignant melanocytes, such as insulin-like growth factor-1 receptor (IGF1-R), FGF-R1, HER2/NEU and FAK, are likely to play a role in melanoma genesis and progression.