Objective: We describe the patient with ophthalmoparesis, visual loss and ataxia suspected of Sjogren9s, whose symptoms improved with steroids and IVIg but evolved into severe ataxia, weakness and systemic symptoms consistent with POEMS, which lead to diagnosis of diffuse large B-cell non-Hodgkin9s lymphoma. Background Lymphoma and related lymphoproliferative disorders may involve peripheral nerves on immunological or infiltrative basis long before known malignancy. Examples include non-Hodgkin and Hodgkin9s lymphoma, CLL, Waldenstrom9s macroglobulinemia, and osteosclerotic myeloma. Different phenotypes of neuropathies associated with lymphomas are likely due to circulating monoclonal anti-nerve antibodies secreted by tumor cells, usually immunoglobulin-M paraproteins directed at specific antigens such as the ganglioside GM1 and myelin-associated glycoprotein. Design/Methods: Previously healthy a 61- year-old man developed visual disturbance and gait imbalance that improved initially with oral steroids and IVIg. Three months later, he became diffusely weak and ataxic, and did not respond to IVIg and later on to plasma exchanges with IV steroids. Diagnostic work up of neuropathy and weight loss was initially consistent with Sjogren9s and suggestive of POEMS, which prompted bone marrow and lymph node biopsies. Results: Markedly elevated SS-A/ SS-B and IgM GM1 antibodies with IgM monoclonal paraprotein lambda light chain were identified in serum, while VEGF was normal. Lip biopsy was consistent with Sjogren9s. Skeletal survey was negative for osteosclerotic lesions, while CT scans revealed diffuse lymphadenopathy. Subsequent bone marrow and lymph node biopsies were consistent with transformed marginal zone lymphoma. Repeated lymph node biopsy showed more aggressive diffuse B-cell lymphoma. Three courses of cyclophosphamide, dexamethasone, rituximab and doxorubicin resulted in marked clinical improvement. Conclusions: IgM monoclonal gammopathy and Sjogren9s-associated neuropathy may herald associated malignancy of B-cell lineage, and it can be refractory to immunotherapies but responsive to chemotherapy. Transformation of indolent marginal zone into more aggressive diffuse large B-cell lymphoma has less favorable prognosis and may require hematopoietic stem-cell transplantation. Disclosure: Dr. Snapp has nothing to disclose. Dr. Ambrose has nothing to disclose. Dr. Kremens has received personal compensation for activities with Teva Neuroscience, Novartis, Allergan, Inc., GlaxoSmithKline, Inc., and General Electric Healthcare. Dr. Marmura has received personal compensation for activities with NeurogesX and Iroko as a consultant. Dr. Marmura has received research support from Merck. Dr. Rakocevic has nothing to disclose.