Despite recent improvements in standard pharmacologic treatments of multiple myeloma (MM), immunotherapy may prove to be more effective due to its higher specificity and lower toxicity. A novel cancer/testis antigen, ropporin, is a testis-specific protein localized in the sperm flagella. Comparing ropporin expression in healthy and MM samples, we did not detect ropporin expression in the normal tissues, but positive signals were found in 44% of the MM primary samples. The immunogenicity of ropporin was confirmed by the presence of specific antibodies detected by enzyme-linked immunosorbent assay in patients' serum. Our results show that ropporin is a novel cancer/testis antigen for MM. Except for in the testis, an immune privileged site, ropporin was not expressed in normal tissues, but was present in MM cell lines and patients' samples. Noteworthy, we show for the first time that ropporin was present at the cell surface of MM plasma cells. We suggest that ropporin is a promising target for MM immunotherapy, as we were able to generate human leukocyte antigen class I-restricted cytotoxic lymphocytes able to kill autologous MM cells.