ObjectiveTo improve the understanding, diagnosis and treatment of special clinical characteristics of Waldenstrom macroglobulinemia (WM). MethodsWe described one case of WM which initially presented with jaundice, and discussed the clinical characteristics, diagnosis and therapeutics based on the literature review. ResultsWM is a B-cell lymphoproliferative disorder characterized by an immunoglobulin M (IgM) monoclonal gammopathy and bone marrow infiltration by lymphoplasmacytic lymphoma, which generally affects elderly patients. WM with primary jaundice is rare in clinic, which is usually misdiagnosed and has missed diagnosis. Patients should have their IgM monitored first before accepting therapeutic regimen including rituximab in order to avoid IgM flare or related complications. ConclusionsThe potential diagnosis of malignant plasma cell disorder should be considered for those patients who presented with jaundice initially, after liver system diseases are excluded. Liver biopsy and related examinations are necessary without delay. Prophylactic plasmapheresis is an active means to lower the incidence of IgM flare, especially for patients with a pre-therapy IgM level of higher than 50 g/L.