Several studies investigated possible associations between single nucleotide polymorphisms and the temperament and character inventory (TCI) scores. The possible association between TCI scores and the estrogen receptors 1 (ESR1) polymorphisms, which are expressed in cerebral regions that are involved in the development of temperament and character, has not been investigated yet. The aim of the present study is to investigate possible associations between specific ESR1 polymorphisms and TCI scores. Two hundred eighty-nine healthy subjects and 111 suicide attempters were enrolled in the study. All subjects compiled TCI. Rs827421, rs1913474, rs1801132, rs722207, rs974276, and rs910416 in ESR1 were genotyped. Rs722207 was associated with Harm Avoidance (HA) in the healthy sample (P = 0.003). Further associations have been found for two HA subscales, HA2 and HA3, in the healthy sample. Additionally, the haplotype rs722207–rs974276 showed an association with HA (P = 0.0003) and HA2 (P = 0.0002) in the global sample and in healthy volunteers and HA3 showed an association in the global sample. Our study showed a moderate association between ESR1 variants and TCI scores. The main finding concerns the association between rs722207 and HA in the healthy sample. Further research is needed to replicate our findings and to investigate further ESR1 polymorphisms. © 2008 Wiley-Liss, Inc.