Recently, a common somatic mutation, A-to-G transition at nucleotide 908, in the estrogen receptor-alpha (ERalpha) gene has been reported. This mutation causes an amino acid change in the ER hinge domain (lysine 303 to arginine, K303R) and confers an increased sensitivity to estrogen and an increased cellular proliferative potential. This mutation has been observed more frequently in breast cancers than in premalignant lesions. According to the previously published reports, the mutation was found in 62% of invasive breast cancers, 85% of the node-positive tumors, and 30% of proliferative breast hyperplasias in the study of US women. The purpose of our study was to investigate whether or not this mutation is present in breast cancers found in Japanese women. We performed mutation analysis using the genomic PCR and direct sequencing in 101 cases of breast cancer and eight cases of benign breast lesions. No K303R mutation was found in the ERalpha gene in these breast lesions obtained from Japanese patients.