Emerging evidence indicates that 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) are useful imaging modalities for evaluating tumor progression in transgenic mouse models of solid human cancers, but the potential of integrated FDG-PET/CT for assessing tumor development in genetically engineered mouse models of liquid human cancers - including neoplasms of immunoglobulin (Ig)-producing plasma cells - has not been established. Here we use a double-transgenic strain of laboratory mice, designated C.IL6Myc, that recapitulates key features of human plasma cell myeloma (a.k.a. multiple myeloma [MM]) to demonstrate that FDG-PET/CT affords a useful research tool for assessing plasma cell tumor (PCT) development in a serial, objective and, importantly, stage- and lesion-specific manner. Supported by serum biomarker analyses (Ig level, paraprotein) and histopathological findings in C.IL6Myc mice undergoing PCT development, the newly generated FDG-PET/CT data set demonstrates the potential of this imaging modality for preclinical basic and translational MM research. PET imaging of genetically engineered mice in which MM-like tumors arise predictably in an intact immunocompetent microenvironment may facilitate the design and testing of new approaches to the treatment and prevention of MM in humans.