The DNA content of plasma cells (DNA Index or DI) was determined after Feulgen reaction using computed image analysis in 46 patients with multiple myeloma at diagnosis. Aneuploidy was found in 4046 (87.0%) patients; 27 (58.7%) were hyperdiploid (DI = 1.05–1.45), 11 (24.0%) were hypodiploid (DI = 0.90–0.95), and two (4.3%) were biclonal. Cytogenetic study showed at least one abnormal mitosis in 2146 (45.7%) cases. All patients with numeric changes had aneuploid DI, and thus confirmed DI ≥ 1.05 and DI ≤ 0.95 as good limits for aneuploidy with image analysis. Since abnormal karyotypes were observed mainly in stages II and III (55.6% and 54.5%, respectively) rather than in stage I (26.7%), aneuploid DI was found in most patients in all three stages, namely in all 1515 (100%) patients in stage I. The prognostic value of aneuploidy was difficult to ascertain in our series. Hypodiploidy or DI > 1.15 was not especially associated with aggressive disease, as it was observed in 715 patients in stage I; however, with the same limits, patients with stages II and III were refractory to first-line chemotherapy. Image analysis is a highly sensitive method showing aneuploidy in most patients with MM at diagnosis and, in association with cytogenetic study, may help to better understand the pathogenesis of the disease. The independent prognostic value of aneuploidy was not fully established in this report.