We present a cytogenetic and fluorescence in situ hybridization (FISH) study, using centromeric probes for chromosomes 3, 7, 11, and 18, TP53 gene (17p13), and RB-1 locus (13q14) DNA probes, in four cases of plasma cell leukemia (PCL). Among the four cases, three presented monosomy of the RB-1 locus and one monoallelic deletion of the TP53 gene. The present report shows the usefulness of the FISH technique to detect abnormalities not previously observed by conventional cytogenetics.