Various diffusion-based approaches were suggested for the characterization of lesional tissue in MS-patients. The multi-compartment spherical mean technique (SMT) has been proposed as a way to investigate microscopic diffusion properties in multiple water compartments. However, the potential of SMT for lesion characterization remains unclear. We investigated diffusion-based SMT properties in active and chronic lesions in 58 MS patients and related them to conventional diffusion tensor imaging (DTI). We found that SMT allows a more specific characterization of MS-lesions than DTI and provide evidence that SMT can be considered as a sensitive and robust measure for myelin content in MS patients.