A combination of cytoplasmic immunofluorescence to detect the immunoglobulin light chain and an interphase fluorescence in situ hybridization technique was used to study the recurrent genetic abnormalities in 14 patients with plasma cell leukemia (PCL). Of the 14 patients studied, 5 had primary and 9 secondary PCL. Chromosomal abnormalities were detected in all 14 patients (100%). Deletions of 13q14 were detected in 11 (78%) cases and deletions of 17p13.1(TP53) in 6 (43%) cases. Translocations (11;14), (4;14), and (14;16) were found in 5 (35%), 2 (14%), and 1(7%) cases, respectively. Except for an association between t(4;14) and 13q14 deletions, no association was identified among the genetic abnormalities. Our study revealed that recurrent genetic changes are more frequent in PCL than in multiple myeloma. The frequent TP53 deletions may represent a marker of genetic instability giving rise to an increased propensity for myeloma cells to emigrate from the bone marrow environment and enter leukemic phase.