In the case of esophageal adenocarcinoma lesion, differential diagnosis to establish the putative primary origin takes into consideration the lung, in which cells frequently express the thyroid transcription factor 1 (TTF-1), and breast adenocarcinomas, which are generally positive for estrogen receptor (ER), mammaglobin, gross cystic fluid protein and GATA3. The gene discussed is ESR1; the disease is breast adenocarcinoma.