A second model has been described for the melanoma cell line RMS, derived from spontaneously arising skin tumors in Ret transgenic mice,18 which after subdermal injection yields brain metastasis 3–6 months after surgical removal of the primary tumor in 23% of injected mice.9 Isolation of and subsequent culture of cells from these spontaneous melanoma brain metastasis gave rise to a brain-trophic cell derivate of the RMS cell line, developing brain metastasis in 64% of mice upon subdermal re-injection.19 The gene discussed is RET; the disease is melanoma.