Multiple myeloma is a B-cell neoplasm characterized by the monoclonal proliferation of plasma cells in the bone marrow, the development of osteolytic lesions, and the induction of angiogenesis. These different processes require three-dimensional interactions, with both humoral and cellular contacts. The 5TMM models are suitable to study these interactions. These are murine models that originate from spontaneously developed myeloma in elderly mice. They are propagated by in vivo transfer of the myeloma cells into young syngeneic mice. We report methods involving the maintenance of the 5T2MM model and the quantification of tumor burden (by determining serum paraprotein concentration and plasmacytosis), assessment of bone lesions, and quantification of angiogenesis. The combination of these different techniques in these models not only helps in unraveling basic biological processes but also in the testing of potentially new therapeutic targets.