Genetic and environmental factors are thought to play roles in the etiopathology of fibromyalgia syndrome (FMS). The objective of this study was to determine the potential effects of single nucleotide polymorphisms (SNPs) in catechol-O-methyltransferase (COMT) (rs4680) and 5-hydroxytryptamine (serotonin) 2A (5-HT2A) receptor (rs6313 and rs6311) genes on susceptibility to FMS. One hundred seventy-one women (80 FMS, 91 control) were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for the genotyping analyses. Genotype and allele frequencies were calculated by the chi-square test. Beck depression inventory, state and trait anxiety inventory and symptom checklist-90 revised (SCL-90-R) tests were applied to both patients and controls. There were no observed differences in the frequencies of alleles and genotypes between patients and controls for the COMT, and the two 5-HT2A receptor gene polymorphisms (P > 0.05). Our results suggest that the investigated polymorphisms seem not to be the susceptibility factors in etiology of FMS.