A 53-year-old woman was admitted to our hospital with left chest-wall pain. Computed tomography scans showed a homogenous mass on the left chest-wall with pleural effusion. Laboratory data showed anemia, hypercalcemia, and high levels of serum IgG. An IgG-lambda monoclonal protein was detected with serum immunoelectrophoresis. In addition, the serum level of neuron specific enolase (NSE) was elevated. A chest-wall tumor biopsy and a bone marrow aspiration revealed diffuse proliferation of atypical plasma cells, which were positive for cytoplasmic CD38 and IgG-lambda. The patient was diagnosed as having IgG-lambda type multiple myeloma with a chest-wall plasmacytoma. Immunostaining revealed diffuse NSE staining in the cytoplasm of the atypical plasma cells. These findings suggested that the myeloma cells produced NSE. The left chest-wall tumor and bone marrow myeloma cells disappeared following several courses of chemotherapy and radiotherapy and the serum levels of IgG and NSE also normalized. No recurrence of the multiple myeloma was seen after an autologous peripheral blood stem cell transplantation. This is the second report of an NSE-producing multiple myeloma. Interestingly, our case has similar clinical phenotypes with the previously reported case, such as chest-wall plasmacytoma, pleural effusion and hypercalcemia.