A recent association study has provided evidence that chromosome 10q22.1 may contain candidate genes for multiple sclerosis (MS). We analysed two intronic and a non-synonymous single nucleotide polymorphism (SNP) of the C10orf27 gene in 571 patients with MS (relapsing remitting and primary progressive) and healthy controls. Adjusted comparisons revealed significant association with disease susceptibility for one intronic SNP in RRMS individuals and the amino acid modifying SNP for PPMS cases; the latter may also contribute to faster disease progression. Transcript expression in brain lesions from MS patients was increased. These findings suggest C10orf27 as a candidate gene for MS susceptibility and pathogenesis.