Adenocarcinoma of the breast is frequently positive for estrogen receptor, while adenocarcinoma of the lung is frequently positive for thyroid transcription factor 1 (TTF-1) and napsin A. ICC is essentially negative for these markers; thus, these markers are useful for differentiating between ICC and hepatic metastasis of breast cancer and lung cancer. The gene discussed is ESR1; the disease is intrahepatic cholangiocarcinoma.