Monoclonal gammopathy is observed in approximately 10% of patients with peripheral neuropathy, which is particularly common in those with the immunoglobulin M monoclonal component. The diagnostic challenge lies in determining whether the neuropathy is causally related to the paraprotein or merely coincidental. Physicians must be familiar with the spectrum of monoclonal gammopathy–associated neuropathies, including anti–myelin-associated glycoprotein neuropathy, amyloid light chain amyloidosis, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, IgM paraprotein, cold agglutinins, and disialosyl antibodies), and cryoglobulinemia, as well as their clinical, electrophysiologic, and immunologic characteristics. Initial workup includes serum protein electrophoresis, immunofixation, free light chain analysis, and targeted antibody testing based on the paraprotein and neuropathy phenotype. Close collaboration between neurologists and hematologist-oncologists is essential for accurate diagnosis and appropriate treatment, which may involve both immunotherapy and targeted therapies for the underlying hematologic disorder.

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