In this study, AREG enriched MM1.S multiple myeloma cell and multiple myeloma patient-derived bone marrow EVs promoted both RAW 246.7 and primary human CD14+ cell osteoclast differentiation, through EGFR activation, a 1.5-fold increase in MM9 protein expression and an increase in TRAP staining. This evidence concerns the gene EGFR and plasma cell myeloma.