We used two indirect approaches [image analysis (Feulgen staining) and fluorescence in situ hybridization (FISH)] to study bone marrow plasma cells (BMPC) in 28 patients fulfilling criteria for MGUS. 61% of patients were found to be aneuploid after image analysis: three were hypodiploid and 14 were hyperdiploid. 12/14 hyperdiploid patients also revealed abnormalities after FISH: 12-72% of BMPC exhibited trisomy for at least one of chromosomes 3, 7, 9 and 11. These latter chromosomes are the four chromosomes most frequently implicated (in the shape of trisomy) in MM, confirming the tight relationship between both conditions. After a median follow-up of 19 months (12-41 months) no patient developed overt MM. Also, we failed to find any relationship between currently available biological parameters and DNA findings. As literature data give a transformation rate of 20-30% after a follow-up of 20-35 years, it is worth presuming that some aneuploid patients will evolve to MM, whereas others (also with aneuploid bone marrow plasma cells) will never develop cancer. Our findings indicate that numeric abnormalities, as they are shared both by MGUS and MM patients, are certainly an additional or a prerequisite event, but are not related to an overt disease. They also emphasize the importance of cytogenetic study in the pathophysiology of MGUS.