New very high permeability dialysis membranes have been developed to enable the clearance of free light chains in myeloma cast nephropathy. These new dialysis techniques, in combination with chemotherapy, should allow improved prognosis in patients with myeloma cast nephropathy. We report a prospective observational study comparing patients who underwent hemodialysis in our center in 2009 for cast nephropathy revealing multiple myeloma vs. patients treated for the same condition during the same period in other centers in our region. The main difference in the management protocols was the use of high cutoff (HCO) membranes in our center. We described the clinical features, the management protocols, and the outcomes as of June 1, 2010. In 2009, five patients were treated for myeloma cast nephropathy with HCO hemodialysis in our center. At 386 ± 100 days follow-up, one patient died, while three of the five patients recovered their renal function, allowing cessation of hemodialysis. During the same period, five patients were treated for myeloma cast nephropathy in other centers in our region. At 398 ± 131 days follow-up, four patients died, and none of the patients recovered renal function, allowing cessation of hemodialysis. In our study, light chain clearance allowed recovery of renal function and cessation of hemodialysis in three of five patients with acute kidney injury secondary to myeloma cast nephropathy. A randomized trial comparing this technique with conventional hemodialysis techniques should be conducted to raise the level of proof for this therapeutic option. The overall prognosis, including quality of life and cost-effectiveness, of HCO hemodialysis should also be examined.