We monitored the behavior of residual myeloma plasma cells in patients with multiple myeloma after high-dose therapy and autologous or allogeneic transplantation using 3 methods of a flow cytometric technique using 4-color staining, immunofixation, and polymerase chain reaction approaches. We analyzed 17 cases by a relatively simple flow cytometric technique using CD38/CD45/CD19/CD56. Detectable myeloma plasma cells were found in 5 patients at diagnosis and 9 patients after treatment. Of 14 cases, 9 (64%) had CD19-CD56+ myeloma plasma cells, and 5 (36%) of 14 had CD19-CD56- myeloma plasma cells. When 37 bone marrow samples that had less than 5% myeloma plasma cells were assessed, myeloma plasma cells were detected in all 20 immunofixation-positive cases and 3 of 17 immunofixation-negative cases (P = .002). All 4 polymerase chain reaction-negative samples characterized as immunofixation-negative contained no detectable myeloma plasma cells. Flow cytometry can provide effective information to detect low levels of myeloma plasma cells.