Background <p>Cryoglobulins are abnormal immunoglobulins present in circulation, capable of precipitating at lower temperatures and redissolving upon rewarming to body temperature (37&#xa0;°C). It is widely accepted that mixed cryoglobulinemia is more commonly seen in chronic infections and autoimmune diseases. Here, we present a case of cryoglobulinemic nephritis due to Monoclonal Gammopathy of Renal Significance.</p> Case presentation <p>The patient was a 60-year-old male who presented with “bilateral lower limb edema for one month.” Clinical features included purpura on the lower extremities, proteinuria, and renal insuff iciency. Laboratory findings revealed a decrease in serum complement C4, a positive rheumatoid factor, and the presence of an IgMκ monoclonal immunoglobulin in serum immunofixation electrophoresis. Bone marrow biopsy revealed a plasma cell proportion of 2%. Renal biopsy analysis demonstrated membranoproliferative glomerulonephritis under light microscopy, with predominant deposition of IgM and κ chains on immunofluorescence. Although electron microscopy did not reveal highly ordered microtubules or ring-like structures typically associated with cryoglobulins, the qualitative test for cryoglobulins was positive. Given the diagnosis of cryoglobulinemic nephritis due to Monoclonal Gammopathy of Renal Significance, the patient was treated with a combination of prednisone, rituximab and cyclophosphamide. Follow-up showed significant improvement in proteinuria and immunological indicators, and renal function stabilized.</p> Conclusions <p>When renal pathology suggests cryoglobulinemia, cryoglobulin testing and electron microscopy examination should be performed, and hematological related examinations should be completed to clarify the etiology. If the patient’s response to rituximab alone is poor, combination immunosuppressive therapy may be considered.</p> Clinical trial registry number <p>Not applicable.</p>