BACKGROUND: Peripheral neuropathy can be associated with certain monoclonal gammopathies; therefore, monoclonal protein testing is routinely performed in the evaluation of this symptom. However, limited data exist regarding the utility of monoclonal protein testing for this indication. Data suggest those receiving a new monoclonal gammopathy of undetermined significance (MGUS) diagnosis have similar rates of diagnosis-related anxiety when compared to those receiving a myeloma diagnosis (Maatouk et al., Blood Cancer J 9(2), 2019; Adami et al., Eur J Clin Invest 49(3), 2019; Rögnvaldsson et al., Blood Cancer J 11(5):1-13, 2021). OBJECTIVE: To quantify the utility of monoclonal protein testing with respect to early detection of malignancy or determining etiology of peripheral neuropathy. DESIGN/PARTICIPANTS: We reviewed records of patients who received monoclonal protein testing for neuropathy as per ICD-10 codes at our institution during 2021 (n=1436). All those with previously diagnosed monoclonal gammopathies were excluded (n=37). Clinical utility was defined as finding a new lymphoplasmacytic neoplasm diagnosis, or if the neuropathy was ultimately attributed to the monoclonal gammopathy identified with testing. KEY RESULTS: Among 1399 patients receiving monoclonal protein testing, 148 (10.6%) were diagnosed with monoclonal gammopathy, the majority (98.6%) being MGUS. As a result of monoclonal gammopathy screening, neuropathy was ultimately attributed to monoclonal gammopathy in 12 patients (0.8% total), and two patients (0.1%) were diagnosed with a lymphoplasmacytic malignancy as a result of monoclonal protein testing. CONCLUSIONS: In the evaluation of peripheral neuropathy, routine monoclonal protein testing has low clinical utility. In our study, greater than 1 in 10 patients screened were diagnosed with MGUS, while less than 1 in 100 patients were determined to have neuropathy attributable to monoclonal gammopathy. Our data suggest the test performance of monoclonal protein testing for the indication of peripheral neuropathy without other findings to suggest an underlying paraproteinemic process, such as bony pain, renal dysfunction, or unexplained anemia, is poor, and this test should be reserved for individuals in whom alternative diagnoses are first considered and excluded.