Objective To analyze the morphology, immunophenotypes, cytogenetics and molecular biology (MICM) abnomaities of Waldenstrom macroglobulinemia (WM). Methods Clinical data of 41 patients with newly diagnosed WM from 1999 to 2010 were collected and studied retrospectively (including 27 males and 14 females). Their clinical manifestations, cell morphology in bone marrow, immunophenotypes, and cytogenetics, immunoglobulin heavy chain gene rearrangement, and expression of preferentially expressed antigen of melanoma (PRAME) were examined by G-banding and FISH, PCR-IgH and RQ-PCR-PRAME and MAGE C1/CT7, and the results were analyzed with clinical prognosis. Results The incidence of high risk patients accounted for 58.5%. Their imunnophenotypes was 100.0% positive to CD19, 97.6% positive to CD20, 74.1% positive to CD38, 36.9% positive to FMC7, 10.0% positive to CD5, 31.6% positive to CD23, 83.3% positive to HLA-DR, and 85.7% positive to CXCR4. There were specific cytogenetic abnormalities found by G-Banding and FISH. RQ-PCR-PRAME had high quantities in WM, which was related to the number of lymphocyte in bone marrow. The MAGE C1/CT7 was negatively expressed in WM. There was no significant survival difference between the Rituximab containing regimen and COP (cyclophosphamide combined with vindisine and prednisone) in treatment of WM. Conclusion WM has specific MICM characteristics. Integrating those measures is helpful to diagnose WM as early as possible, and to monitor the disease during the treatment. Rituximab has no survival benefit in this cohort of patients.