Wen et al have generated a mouse that models one of the leading genetic lesions present in myeloma, NRAS^Q61R, pushing MGUS toward a more aggressive stage of the disease. However, several other genetic lesions have so far eluded modeling. These alterations, central for the development of the disease, are present as early as in the MGUS phase, including hyperdiploidy and several hallmark chromosomal translocations, which deregulate the expression of various genes (cyclins, MMSET, MAF, and others), or appear in later stages of the disease, elicited by somatic mutations or copy number aberrations, affecting a large number of oncogenes and tumor-suppressor genes.