Consisting of a variety of T or B-cell lymphoblastic (ALL) and myeloid (AML) malignancies, zebrafish leukemia is typically modeled through the expression of a frequently mutated proto-oncogene (such as c-Myc [1•], TEL-AML [4] and NOTCH1 [6]) under the rag2 promoter in developing lymphocytes. The gene discussed is NOTCH1; the disease is acute myeloid leukemia.