Purpose: Microsatellite instability (MSI) occurs as a result of sliding in the DNA sequences from shortening or elongation of the repeat zones of DNA during replication. Such abnormalities can normally be corrected by the enzymes coded by the DNA mismatch repair (MMR) genes. Therefore, detection of MSI is considered to be a sign of disorder of the MMR genes and is interpreted as a replication error phenotype. Patients and Methods: We evaluated the MSI in 5 different loci in the 14q32 region of immunoglobulin heavy chain IgH gene in 26 newly diagnosed patients with multiple myeloma (MM). Results: Fifty-four percent of the patients disclosed MSI and at least 1 locus but no significant association of MSI was found between different clinical stages and the MM subtype. MSI was not found in 5 light-chain myeloma patients. Conclusion: Although our case number is small, probably the genomic instability in heavy-chain MM may be a common finding and probably plays a critical role in the MM pathogenesis.