The aim of this study was the evaluation of the erythrocyte deformability in multiple myeloma (MM). We enrolled 29 MM patients and we evaluated, on fasting venous blood, the erythrocyte deformability, expressed as elongation index, and examined using the diffractometric method. By comparing normal controls and MM patients, a significant decrease in erythrocyte deformability, especially at low shear stresses, was found. In this research paper we evaluated all the hypothesis for a possible explanation of the behaviour of red blood cell deformability in MM, even considering how the alteration of erythrocyte deformability worsens the microcirculatory flow in these patients in association with the marked increase in plasma viscosity.