The bone marrow of 47 patients with multiple myeloma (MM), 2 patients with plasma cell leukemia, and 11 patients with monoclonal gammopathy of undetermined significance (MGUS) was analyzed by flow cytometry for the detection of DNA aneuploidy. The question to be addressed was whether a correlation exists between the incidence of DNA aneuploidy and the stage of disease. With one-parameter analysis of DNA staining, a DNA aneuploidy was detectable in 17 of 60 patients. The detection rate for DNA aneuploidies could be increased to 37 of 60 patients with the second method, the simultaneous measurement of DNA content in additional immunophenotyped cells (CD38 or B-B4). In MGUS and the early stages of MM, the discrepancy between both methods was higher than in stage III MM. There were no statistical differences in the incidence of DNA aneuploidy between MGUS or the early stages of MM and stage III MM (21/32 patients vs 16/26 patients). The CD56 expression in plasma cells was significantly higher in cases of DNA aneuploidy (mean +/- SD, 64.7% +/- 33.65% vs 39.3% +/- 36.69%; P = .028). Comparing the ratio of diploid to DNA aneuploid with that of CD56+ to CD56- plasma cells, a correlation was found in MGUS (r = 0.7320) in the early stages of MM, I and II (r = 0.8023), but not in stage III MM. Based on these data, the dual-staining method for DNA content in immunophenotyped cells is preferred for the detection of DNA aneuploidy, especially in the early stages of MM and in MGUS. The clinical importance of a classification of DNA aneuploidy and CD56 antigen expression together is proposed for testing.