Deletions or monosomy of chromosome 13 are frequent in multiple myeloma (MM). A candidate tumor suppressor gene might reside telomeric of the retinoblastoma gene (RBl) at band 13q14 and to play a role in B cell neoplasm. The D13S319 locus, between RB1 and D13S25 loci at 13q14 is the most commonly deleted marker in chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL). We evaluated the D13S319 locus in 24 MM cases by fluorescence in situ hybridization (FISH). We observed monosomy for D13S319 in 6/20 (30%) MM patients with an apparently normal karyotype. As expected, in four karyotypically abnormal MM cases with partial or complete monosomy for chromosome 13, all of them had monoallelic loss of D13S319. Our results indicated that the loss of D13S319 is commonly found in MM, even at diagnosis, and is more frequent than predicted based on conventional cytogenetic analysis of metaphase spreads. This finding implicates a candidate tumor suppressor gene at 13q14 in the pathogenesis of MM.