Monoclonal gammopathies of undetermined significance (MGUS) are characterized by the presence of a monoclonal protein in serum in quite asymptomatic patients. Ten to 33% of MGUS patients eventually will develop overt multiple myeloma, but no single laboratory test exists that can predict changes toward a malignant evolution. The aim of the present study was to apply conventional cytogenetics, the MAC (morphology, antibody, chromosome) method and fluorescence in situ hybridization (FISH) techniques in a series of 50 MGUS patients and 4 "smoldering" multiple myeloma patients to test the usefulness of their approaches as predictive methodologies. All patients studied by conventional cytogenetics presented a normal karyotype independent of the culture conditions used. The MAC method revealed that all mitotic cells showing a normal karyotype were positive for anti-MOP7 or anti-CD3 in 12 patients studied. In addition, two of them presented a numerical abnormality detected by FISH. Using a FISH technique with direct labeled centromeric probes for chromosomes 3, 7, 11, and 18 we showed a numerical abnormality in eight of 35 patients (23%) with a normal karyotype. The common occurrence of MGUS and the fact that they may evolve toward lymphoproliferative disorders displays the importance of being able to identify laboratory results that are capable of predicting the evolution of these patients. In the literature, patients who presented an IgA peak of immunoglobulin type have been associated with a higher risk of evolving to a malignant condition. Our study shows the correlation of MGUS patients who presented monosomy 18 with the presence of an immunoglobulin peak of the IgA type. Prospective follow-up is needed to evaluate the clinical value of monosomy 18 as a predictive factor for defining a high risk of malignant transformation in MGUS patients.