In this study, we have investigated the mRNA expression of the cancer germ‐line genes MAGE, BAGE, GAGE, RAGE and the tumor‐overexpressed gene PRAME by human myeloma cell lines and malignant plasma cells from patients with multiple myeloma (MM). By reverse transcription‐PCR, we show that all myeloma cell lines (n = 16) express at least one of these genes, except RAGE‐1 that was never expressed. We show that malignant plasma cells from the majority of MM patients (n = 21) expressed MAGE‐1, MAGE‐3 and PRAME. On the contrary, polyclonal reactive plasma cells did not express any of these genes. By flow cytometry, we show that mage‐1 protein is expressed within myeloma cells and cell lines and that anti‐mage‐1.HLA‐A1 cytotoxic T lymphocytes efficiently killed MAGE‐1⁺HLA‐A1⁺ MDN myeloma cells. Taken together, our data show that mage‐1 and mage‐3 could constitute specific targets for tumor immunotherapy of MM patients.