Estrogen receptor-beta (ER-B) has been identified in benign and malignant tissues of a variety of human organs including the colon. In breast carcinoma, ER-B was found to be a significant predictor of response to adjuvant hormonal therapy with tamoxifen. The aim of the present study was to determine whether esophageal adenocarcinoma, and its precursosr, Barrett's metaplasia, express ER-B. Sections of formalin-fixed and paraffin-embedded tissue from 31 esophagectomy specimens were immunostained for ER-B using the immunoperoxidase technique, and the percent of positive cells in areas of Barrett's metaplasia negative for dysplasia (ND), low-grade dysplasia (LGD), high-grade dysplasia (HGD) and adecocarcinoma, (CA) were recorded. Nuclear ER-B staining in >50% of the cells was seen in all 23 CA (100%), 10 out of 11 (91%) HGD, 8 out of 11 (83%) LGD and in 10 of 15 (66.6%) ND. It is concluded that all adenocarcinomas of the esophagus and most precursor lesions, Barrett's Metaplasia (BM) with or without dysplasia, express ER-B in a significantly high percentage of the cells. These findings raise the possibility that esophageal adenocarcinomas may benefit from treatment and/or chemoprevention with antiestrogens, such as tamoxifen.