In the MM PrEDiCT (Progression through Evolution and Dissemination of Clonal Tumor Cells) model, human myeloma cell lines are injected into an isolated mouse bone, which is then implanted subcutaneously into an immunodeficient SCID-beige mouse. The implanted bone graft provides the crucial bone marrow microenvironment for the growth of the myeloma tumor cells in vivo. The labeling of individual myeloma tumor cells, with either a fluorescent tag system or via lentiviral DNA barcoding, enables tracking of the growth and dissemination of individual tumor cells and their progeny in an in vivo setting. Gene expression analysis of the primary and disseminated tumor in this model can reveal clinically relevant genes that may play an important role in the pathogenesis of myeloma. See the visual abstract in the article by Shen et al that begins on page 2360.