Rs1132200 was indicated in literature as being associated with susceptibility to multiple sclerosis (International Multiple Sclerosis Genetics C, 2010) while rs17281647 polymorphism was selected on the basis of in silico analysis as Tag SNP that covers one of the linkage disequilibrium (LD) blocks of TMEM39A. Additionally, we conducted a case–control study (on 336 patients and 322 controls) to find a possible association of the investigated polymorphisms with susceptibility and/or progression of MS in a well-defined Polish population. The gene discussed is TMEM39A; the disease is multiple sclerosis.