Three hundred seven patients with MS and 300 controls were genotyped for G98T and A561C SNPs in the E-selectin gene, and genetic data were correlated with the course of the disease. The frequency of the T/T genotype of the G98T SNP was significantly increased in RR-MS patients compared with controls, while was absent in PP-MS. The frequency of the A561C SNP was significantly decreased in SP-MS compared with benign RR-MS. The T/T genotype of the G98T SNP is likely to confer an increased risk to develop MS. The A561C polymorphism seems to act as protective factor towards the progression to SP-MS.