TNF-α and IL-10 single nucleotide polymorphisms have been implicated in various autoimmune diseases but the results are still quite controversial. This case-control study aimed to investigate the association between six TNF-α and five IL-10 polymorphisms with dermatomyositis. The -857CC and +489GG genotypes showed a weak association with dermatomyositis when the analysis was carried out for the whole cohort but they appeared to be a significant risk factor for the development of dermatomyositis in women. The TNF-α -1031CC genotype was found only among dermatomyositis patients. The TNF-α -1031C/-863C/-857C-308G/+489G haplotype showed a significant association with dermatomyositis in women. The IL-10 -3575TT genotype and T allele showed an association with dermatomyositis. The frequency of the IL-10 -2763CC genotype and C allele was higher among dermatomyositis patents and it was associated with an increased OR. Haplotype analysis showed an association between the IL-10 -3575T/-2763C haplotype and dermatomyositis. In conclusion, our results indicate that both TNF-α and IL-10 polymorphisms are associated with the development of dermatomyositis in Bulgarian patients.