Targets of curative donor-derived graft-versus-myeloma (GvM) responses following allogeneic hematopoietic stem cell transplantation (HSCT) remain poorly defined, partly because immunity against minor histocompatibility antigens (mHAgs) complicates the elucidation of multiple myeloma (MM)-specific targets. We hypothesized that syngeneic HSCT would facilitate the identification of GvM-associated antigens since donor immune responses in this setting should exclusively target unique tumor antigens in the absence of donor-host genetic disparities. We therefore studied the development of tumor immunity in an HLA-A0201+ MM patient who achieved durable remission after myeloablative syngeneic HSCT. Using high-density protein microarrays to screen post-HSCT plasma, we identified six antigens that elicited high-titer (1:5,000-1:10,000) antibodies that correlated with clinical tumor regression. Two antigens (DAPK2, PIM1) had enriched expression in primary MM tissues. Both elicited antibody responses in other MM patients following chemotherapy or HSCT (11 and 6 of 32 patients for DAPK2 and PIM1, respectively). The index patient also developed specific CD8+ T cell responses to HLA-A2 restricted peptides derived from DAPK2 and PIM1. Peptide-specific T cells recognized HLA-A2+ MM-derived cell lines and primary MM tumor cells. Coordinated T and B cell immunity develops against MM-associated antigens following syngeneic HSCT. DAPK1 and PIM1 are promising target antigens for MM-directed immunotherapy