Endometriosis and leiomyoma are both common estrogen-related gynaecological diseases. We aimed to elucidate the association of estrogen receptor α (ERα)-351 A>G (XbaI) and –397 T>C (PvuII) gene polymorphisms with endometriosis and leiomyoma. Women were divided into three groups: (i) severe endometriosis (n=112), (ii) leiomyoma (n=106) and (iii) normal controls (n=110). Genomic DNA was obtained from peripheral leukocytes. ERα-351 A/G XbaI and –397 T/C PvuII polymorphisms were assayed by the method of PCR and restriction fragment length polymorphism (RFLP). Genotypes and allelic frequencies in each group were compared. The genotype/allele frequencies of ERα-351 and –397 polymorphisms in endometriosis or leiomyoma groups were different from those of normal controls. ERα mutant-related genotypes/alleles (-351G and –397C) presented higher percentages in the endometriosis/leiomyoma population compared with normal controls. Proportions of ERα-351 AA/AG/GG genotypes and A/G alleles in each group were (i) 26.8/57.1/16.1 and 55.4/44.6%; (ii) 19.8/52.8/27.4 and 46.2/53.8% and (iii) 33.6/64.6/1.8 and 65.9/34.1%. Proportions of ERα-397 TT/TC/CC genotypes and T/C alleles in each group were (i) 24.1/60.7/15.2 and 54.5/45.5%; (ii) 23.6/70.8/5.6 and 59/41% and (iii) 54.5/40/5.5 and 74.5/25.5%. We concluded that ERα-351 XbaI*G- and –397 PvuII*C-related genotypes/alleles were correlated with higher susceptibilities of endometriosis or leiomyoma, which might be associated with related pathogeneses.