Few data are available on the efficacy of the combination of lenalidomide plus dexamethasone (Len/Dex) in very elderly patients above 75 years of age with relapsed multiple myeloma (MM). We report here a single-center series of 45 consecutive patients aged 75 years or older with relapsed MM treated with this combination. The overall response rate was 62% and the median progression-free survival was 14 months, which compares favorably to that described in the two pivotal prospective studies that formed the basis for the approval of Len/Dex in the relapse setting. Our study confirms that Len/Dex is an effective combination in very elderly patients with relapsed MM.