We recently showed that human melanoma cell lines harbour a rare subpopulation of cells that are profoundly deficient in expression of NME1 and NME2 and exhibit greatly enhanced metastatic activity.3 By virtue of their complete ablation of Nme1 and Nme2 expression, HPN1 and HPN2 mice are relevant in vivo models for the NME-deficient and highly metastatic subpopulation in human cells. Here, NME1 is linked to melanoma.