We report a case of a woman, who initially presented with an non-secreting multiple myeloma, 11 months later, she was diagnosed as an IgD-secreting myeloma. In December, 2010, the patient's serum protein quantification and immunofixation electrophoresis (IFE) revealed polyclonal immunoglobulin with no evidence of monoclonal immunoglobulin. However, her bone marrow smears revealed an abnormal proliferation of atypical plasma cells (46.5%), so she was diagnosed as non-secreting multiple myeloma. After three cycles of administration of Velcade plus Dexamethasone (VD), she achieved a complete remission (CR). Unfortunately, on October 31, 2011, our patient was found to have a separate peak of monoclonal component on the.-region of cellulose-acetate electrophoresis, and the serum immunofixation electrophoresis revealed the monoclonal component was IgD. Several months later, she presented with a large swelling of the left side of her neck. Microscopic examination of a biopsy specimen from the cervical mass showed a neoplastic plasma cell tumor and she died on January 28, 2013 from acute respiratory failure resulting from neoplastic plasma cells infiltration and infection. Here we report this rare case and review the literature for similar cases.