Receptor-mediated estrogen activation participates in the development and progression of breast cancer. Estrogen receptor (ER)-alpha polymorphism has been found to be associated with breast cancer and clinical features of the disease in Caucasians. Epidemiologic studies have revealed that age-incidence patterns of breast cancer in Asians differ from those in Caucasians. Genomic data for ER-alpha in either population is therefore of value in the clinical setting for that ethnic group.A case-control study was conducted to establish a database of ER-alpha polymorphisms in a Taiwanese population in order to compare Western and Taiwanese (Asian) distributions and to evaluate ER-alpha polymorphism as an indicator of clinical outcome. The ER-alpha gene was scanned in a Taiwanese clinical breast cancer group (189 patients) and in healthy individuals (177 healthy control individuals). PCR single-strand conformation polymorphism technology was employed and real-time PCR melting curve analysis was performed.Three sites of silent single nucleotide polymorphism (SNPs) were found, as reported previously in Western studies, but at significantly different frequencies. Among the three SNPs, the frequency of allele 1 (TCT --> TCC) in codon 10 was significantly lower in breast cancer patients (32.0%) than in control individuals (40.4%; P = 0.018). We found that allele 1 (ACG --> ACA) in codon 594 was less common in breast cancer patients with a family history of breast cancer (5.9%) than in those without such a history (19.6%; P = 0.049). Individually, both allele 1 in codon 325 (CCC --> CCG) and allele 1 in codon 594 exhibited a reverse association with the occurrence of lymph node metastasis. Furthermore, incorporation of both SNP markers further increased predictive accuracy.Our data suggest that ER-alpha polymorphisms are correlated with various aspects of breast cancer in Taiwan. ER-alpha genotype, as determined during presurgical evaluation, might represent a surrogate marker for predicting breast cancer lymph node metastasis.