Objective: The aim of the study was to investigate the clinic manifestation, diagnosis and treatment on multiple myeloma (MM) with the onset of renal impairment. Methods: The 27 cases of multiple myeloma with the onset of renal impairment were collected in Department of Nephrology, Wuhan General Hospital of Guangzhou Command, China, from January 2007 to January 2011. All cases were divided into the groups with renal dysfunction (n = 16) and normal renal function (n =11). The clinic manifestations, treatments and prognosis of all patients were analyzed. Results: Of all the patients in normal renal function group, 5 suffered nephrotic syndrome, 4 had abnormal results of routine urinalysis (hematuria or proteinuria) which were not caused by nephrotic syndrome, and 1 suffered urinary tract infection. Five pathological specimens of renal biopsy revealed that light chain protein, immunoglobulin and complement C3 were deposited mainly in the glomerular basement membrane and mesangia, tubular basement membrane and arteriolar walls. Two pathological specimens were proved to be renal amyloidosis. Patients with renal dysfunction had poorer prognosis, severer anemia, higher values of serum lactate dehydrogenase (LDH) and β2-microglobulin (β2-MG), worse responses to chemotherapy. Of 16 patients with renal dysfunction,14 (87.5%) were stage III, which were significantly higher than that in the group of normal renal function [63.6% (7/11)]. Of 16 cases with renal dysfunction, 9 were treated with blood purification, and 5 of 9 cases were treated with plasma exchange.Conclusion: Multiple myeloma with the onset of renal impairment was easily misdiagnosed. Hemodialysis concomitant with chemotherapy could contribute to recovery of renal function.