Multiple myeloma (MM) is characterized by a clonal proliferation of malignant plasma cells in the bone marrow secreting a monoclonal immunoglobulin (paraprotein) with specific antigenic determinants, the idiotype (Id), which can be regarded as a tumour‐associated antigen (TAA). In order to analyse the impact of a dendritic cell (DC)‐based vaccine, 11 patients with advanced MM were treated with CD34 stem cell‐derived dendritic cells that were pulsed with Id peptides. Subsequently, the patients received three boost immunizations every other week with a combination of Id and granulocyte–macrophage colony‐stimulating factor (GM‐CSF) (nine patients) or with Id peptide‐pulsed dendritic cells again (two patients). The treatment was well tolerated with no side‐effects. The present clinical study was a proof of concept analysis of dendritic cell‐based vaccines in MM. The capacity of the dendritic cells to activate idiotype‐specific T cells was verified by in vitro stimulation experiments before the vaccination therapy. Immunological effects of the Id vaccination were analysed by monitoring changes in anti‐idiotype antibody titres and idiotype‐specific T‐cell activity. After vaccination, three out of 10 analysed patients showed increased anti‐idiotype antibody serum titres, indicating the induction of an idiotype‐specific humoral immune response. The idiotype‐specific T‐cell response analysed by ELISpot was increased in four out of 10 analysed patients after vaccination, and one patient had a decreased plasma cell infiltration in the bone marrow. In conclusion, five out of 11 patients showed a biological response after vaccination. Thus, our data indicate that immunotherapy with Id‐pulsed DCs in MM patients is feasible and safe. DC generated from CD34⁺ progenitor cells can serve as a natural adjuvant for the induction of clinically relevant humoral and cellular idiotype‐specific immune responses in patients suffering from advanced MM.