Multiple myeloma (MM) and Waldenstrom's macroglobulinemia-like lymphoma (MW) appear spontaneously in C57BL/KaLwRij mice at a frequency of 0.5% and 0.2%, respectively. They can readily be propagated by intravenous transfer of mainly bone marrow or spleen cells into syngeneic recipients. Previous studies demonstrated that these mouse malignant monoclonal gammopathies (MMG) show clinical and biologic features that closely resemble those of the corresponding human diseases and thus could be used as experimental models. We report on cytogenetic analysis of two mouse MW and five MM in vivo cell lines of the 5TMM series propagated in syngeneic mice. These studies demonstrated clonal abnormalities in all cell lines, hyperdiploid karyotype in both MW and one MM lines, and hypotriploidy, hypertriploidy, or hypotetraploidy in the other lines. Structural abnormalities of chromosome 15 were observed in all MM lines. In five MM lines, frequent rearrangements were also found for chromosome numbers 1, 2, 5, and 12. A single chromosomal abnormality, as found in induced mouse plasmacytomas and resembling Burkitt lymphoma, was not found in mouse MM and MW. It was concluded that spontaneously originating C57BL MM of the 5T series is a better model for human MM than pristane-induced BALB/c or NZB plasmacytoma.