Myelomatous tissue from 30 patients was assessed for cytogenetic abnormalities and one-third showed chromosomal deletions, additions, and/or rearrangements. Evidence is presented that those cases with only normal cytogenetics represent metaphase cells of nonmyelomatous tissue. The findings of our abnormal cases when added to the 18 reported in two series by others show unique cytogenetic patterns are present in this disease. From analysis of these 27 banded cases of myeloma, we conclude: (1) cytogenetic abnormalities of myeloma are not random; (2) clonal evolution may be associated with disease progression, however the abnormalities identified late in the disease are similar to those found in early myeloma; (3) cytogenetic aberrations of multiple myeloma differ considerably from those of chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and acute lymphocytic and nonlymphocytic leukemia; and (4) the myeloma karyotype often exhibits one or more of the following: rearrangements involving chromosome 1 and 14, trisomy 3, 5, 7, 9 and 11, and monosomy 8 and 13. These findings have great importance for molecular biologic studies of multiple myeloma.