Chromosomal region 1p22 is deleted in ⩾20% of multiple myeloma (MM) patients, suggesting the presence of an unidentified tumor suppressor. Using high-resolution genomic profiling, we delimit a 58 kb minimal deleted region (MDR) on 1p22.1 encompassing two genes: ectopic viral integration site 5 (EVI5)and ribosomal protein L5 (RPL5). Low mRNA expression of EVI5and RPL5was associated with worse survival in diagnostic cases. Patients with 1p22 deletion had lower mRNA expression of EVI5and RPL5, however, 1p22 deletion status is a bad predictor of RPL5expression in some cases, suggesting that other mechanisms downregulate RPL5expression. Interestingly, RPL5but not EVI5mRNA levels were significantly lower in relapsed patients responding to bortezomib and; both in newly diagnosed and relapsed patients, bortezomib treatment could overcome their bad prognosis by raising their progression-free survival to equal that of patients with high RPL5expression. In conclusion, our genetic data restrict the MDR on 1p22 to EVI5and RPL5and although the role of these genes in promoting MM progression remains to be determined, we identify RPL5mRNA expression as a biomarker for initial response to bortezomib in relapsed patients and subsequent survival benefit after long-term treatment in newly diagnosed and relapsed patients.