Few breast cancer cell lines (MDA-MB-453, BT-474, MDA-231, CN34BrM, SUM1315) have been reported to spontaneously form brain metastasis after orthotopic injection, but not in commonly used host nude mice; Instead the use of more permissive hosts lacking NK-cells, such as NSG or Rag2-/-; Il2rg-/- mice, was necessary.13,14 In a immunocompetent host, Nagpal et al. recently reported a HER2+ breast cancer cell line derived from spontaneous BALB/C mammary tumors, which after orthotopic injection and subsequent resection of the primary tumor avidly metastasizes to the brain (60% of mice).15 This evidence concerns the gene RAG2 and breast cancer.