Introduction: This study aimed to investigate the effectiveness of using serum Free Light Chain (sFLC) together with traditional examination methods in diagnosing Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM), especially in patients with Monoclonal Gammopathy (MG) without hypercalcemia, renal dysfunction, anemia, and bone lesions (CRAB) symptoms, by eliminating the need for bone marrow biopsy (BMb). Methods: A total of 160 patients over 50 years of age with an ESR of 50 mm/h and above were included in the study. Serum Immunofixation Electrophoresis (sIFE) and sFLC levels of these patients were studied simultaneously. Sensitivity and specificity of the sIFE and sFLC for diagnosis of MGUS were estimated by ROC analysis. Results: MG was detected in 36 (22.5%) patients with sIFE and in 30 (18.7%) patients with sFLC of 160 patients included in the study.There were a total of 44 patients with MG detected by sIFE alone, sFLC alone, and both sIFE and sFLC. BMb were performed on 42 patients with MG who approved the BMb procedure. These patients were diagnosed MGUS, SMM and MM by using test results, BMb results, and clinical and laboratory data. The sensitivity of sIFE in the detection of MG was 82.5% and the specificity was 99.2% (p<0.001). sFLC had a sensitivity of 72.5% and a specificity of 99.2% (p<0.001). When sIFE and sFLC were performed simultaneously, the sensitivity was 100% and the specificity was 98.3% (p<0.001). Discussion and Conclusion: Simultaneous monitoring of sIFE and sFLC, which is both non-invasive and with the opportunity to achieve results in less time without BMb, may be sufficient and reliable in the diagnosis and follow-up of MGUS in the detection of MGs and especially in asymptomatic patients