8p21.3 deletion was recently characterized in B cell lymphoma suggesting that TRAIL-R1 and TRAIL-R2 may be the target of the deletion and act as dosage-dependent tumor suppressor genes. As multiple myeloma is a plasma cell malignancy originating from B-lineage clonogenic cells, the idea was why do not evaluate this deletion in this pathology. Thus, interphase FISH studies with two mixtures of probes spanning the 8p21.3 region were retrospectively performed in 37 French multiple myeloma patients. Surprisingly, deletion in this region was found in 8 (21.6 %) patients. Interestingly, this deletion was usually associated with a 13q14 deletion. In two among them, the patients showed also translocation (4;14)(p16;q32) and one other harbor also a deletion of the P53 gene. These results indicate that deletion of TRAIL-R1 and TRAIL-R2 may be relevant to the loss of 8p21.3 and may play an important role the pathogenesis of MM. The association of this deletion with other well-known chromosomal aberrations in multiple myeloma suggests, as previously described, that these anomalies are not randomly distributed, but strongly interconnected.