Objective To analyze the clonal relationship between lymphocytes in peripheral blood (PB) and myeloma cell in bone marrow (BM) for proving the existence of circulating tumor cells in multiple myeloma (MM) patients. Methods Eighteen patients with MM who have no cytomorphologic plasma cells and CyIg cells in PB demonstrated by anti-κ and anti-λ MoAbs using ABC method were involved in the present study, including 3 cases in phases I - II and 15 cases in phase III. The complementary determining region 3 (CDR3) of immunoglobulin heavy chain (IgH) gene was amplified by polymerase chain reaction (PCR). We further analysed the single strand conformation of the PCR products by single strand conformation polymorphism (SSCP) analysis to detect the mononuclear cells in PB and BM of the patients simultaneously. Results The same PCR products of IgH-CDR3 gene with BM samples were found in PB of 11 MM patients. The same PCR products and single strand conformation in both PB and BM were found in 9 cases. Conclusions This study has proved the presence of identical clonal malignant cells in PB and BM of MM patients. B cells are involved in the pathogenesis of MM.