Perhaps the strongest clinical correlation of VEGF/VEGFR dysregulation in angiosarcoma is the finding of VEGFR3 (FLT4) gene amplification in secondary (radiation- or lymphedema- induced) angiosarcomas.7 These amplifications are generally found in combination with other alterations such as c-MYC amplification and mutations in PLCG1 and PTPRB. Thus, although VEGFR3 drives lymphangiogenesis and induces sprouting and tip cell migration, the individual contribution of VEGFR3 amplification in these cases remains unclear. The gene discussed is FLT4; the disease is lymphedema.