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Information is sparse and contradictory in the literature regarding the role of estrogen receptor (ER) and progesterone receptor (PR) in esophageal carcinoma. This study was conducted over a period of 18 months from September 2004 with the primary aim of determining the PR, ER alpha (ERα) and ER beta (ERβ) status of esophageal carcinoma and normal esophageal mucosa (NEM). The receptor status was correlated with tumor type, tumor differentiation and tumor stage. A total of 45 patients with histologically proven squamous cell carcinoma (SCC) (n = 30) and adenocarcinoma (AC) (n = 15) were studied. Receptor status was detected by immunohistochemistry (IHC) and semiquantitative assessment was done by quick score method of endoscopic biopsy specimens. The mean age for SCC and AC were not significantly different. The gender ratio in favor of males was 3: 2 for SCC and 4: 1 for AC. None of the specimens from SCC or AC showed positivity for PR both in NEM and tumor tissue. Likewise none of the specimens were positive for ERα by IHC. The mean ERβ score for AC was significantly higher than SCC. For SCC it was seen that ERβ positivity in tumor cells increases with dedifferentiation and increasing tumor stage. This trend was seen for AC as well. ERβ is over-expressed in poorly differentiated SCC and AC compared to NEM. Thus ERβ may be a marker for poor biological behavior, that is dedifferentiation or higher stage of disease. In view of these findings we propose a large-scale prospective, longitudinal interventional study using selective estrogen modulators.