The etiology of multisomatoform disorder (MSD) is largely unknown, but genetic disposition may be one of several risk factors. As pain is a major component of MSD, and polymorphisms in the catechol-O-methyltransferase (COMT) gene are associated with COMT enzymatic activity and pain sensitivity, we assumed that COMT polymorphisms could be associated with MSD. One hundred and forty-nine patients with MSD and 149 age- and sex-matched healthy controls participated in this study. The inclusion criteria for MSD were in accordance with the structured clinical interview of the diagnostic and statistical manual of mental disorders IV. DNA from MSD patients and controls was genotyped for six single-nucleotide polymorphisms (SNPs) within the COMT locus by polymerase chain reaction and restriction enzyme analysis. The distribution of COMT SNP alleles, genotypes, and haplotypes was compared between patients and controls. None of the investigated SNPs, including the functionally relevant common SNP in codon 158 (Val158Met), showed a statistically significant allelic, genotypic, or haplotypic association with MSD. We conclude that COMT polymorphisms on their own do not seem to play a relevant role as major genetic risk factors for MSD.