Objective: Clinically, the reason of resistance for breast cancer to endocrine therapy has not been well known. The current study attempted to examine loss of heterozygosity (LOH) on the estrogen receptor (ER) gene in breast cancer and its relationship to clinicopathologic findings. Methods: DNAs of tumor tissues and blood lymphocytes were collected from 40 cases of primary breast cancer patients and LOH were detected using the microsatellite repeat assay and combined with other ER immunohistochemical assays. Results: ER-positive staining was observed in 65% of breast cancer. Heterogeneity of ER expression was found. Seven of the patients (17.5%) showed LOH. In three of the seven cases, there was total loss, and there was a marked reduction in the intensity of signal in the other four cases. LOH was associated with histologic grade, occurring more frequently in ER-negative and lymph node metastasis group, but not with tumor size and patient ages. Conclusion: This result implied that LOH of the ER gene may have an important role in the progression of breast cancer. It was postulated that the lack of ER function induced by LOH may contributed to endocrine therapy resistance of breast cancer since the tumor clone would escape from the ER regulation, obtain growth predisposition and finally lost response to therapy. Objective: Clinically, the reason of resistance for breast cancer to endocrine therapy has not been well known. The current study attempted to examine loss of heterozygosity (LOH) on the estrogen receptor (ER) gene in breast cancer and its relationship to clinicopathologic findings. Methods: DNAs of tumor tissues and blood lymphocytes were collected from 40 cases of primary breast cancer patients and LOH were detected using the microsatellite repeat assay and combined with other ER immunohistochemical assays. Results: ER-positive staining was observed in 65% of breast cancer Seven of the patients (17.5%) showed LOH. In three of the seven cases, there was total loss, and there was a marked reduction in the intensity of signal in the other four cases. LOH was associated with histologic grade, occurring more frequently in ER-negative and lymph node metastasis group, but not with tumor size and patient ages. Conclusion: This result implied that LO H of the ER gene may have an important role in the progression of breast cancer. It was postulated that the lack of ER function induced by LOH may contributed to endocrine therapy resistance of breast cancer since the tumor clone would escape from the ER regulation, obtain growth predisposition and finally lost response to therapy.