Transcription factors encoded by PAX3 and PAX7 are amongst the first expressed in the embryo, being principal regulators of neurogenic and myogenic progenitor cell specification and embryonic segmentation. The basis for this review lies in the supposition that genetic programs for cell migration, thought regulated by PAX3 and PAX7 during embryonic development, become tools used by the metastatic cell. In highly metastatic neoplasms arising from cells of neurogenic and myogenic lineages such as embryonal rhabdomyosarcoma and cutaneous malignant melanoma, markedly high expression levels of PAX3 and PAX7 support this supposition. As PAX3 and PAX7 are known to play a role in the regulation of migratory events in embryogenesis, it is possible that the metastatic potential of these tumours is directly linked to migratory properties conferred them through PAX expression. Here we provide a novel perspective by correlating metastasis with expression of PAX3, PAX7 and ephrin/Eph receptors as well as NCAMs, cell surface markers normally involved in migration and adhesion during development, and propose a role for PAX genes in the increased metastatic potential of these tumours.