Esophageal Paget’s disease is very rare. It can occur alone or in combination with invasive adenocarcinoma, squamous cell carcinoma, and adenosquamous carcinoma. A man aged 58 years with a case of esophageal adenosquamous carcinoma with Paget’s disease was reported in Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, who was presented with “progressive food dysphagia with hoarseness for more than 3 months”. Pathological examination showed that the esophageal squamous epithelium, esophageal mucous glands and ducts were extensively involved by Paget cells, and submucosal adenosquamous carcinoma was seen. Immunohistochemistry (IHC) showed that both Paget cells and adenocarcinoma components in invasive carcinoma nests expressed CK7 but not p40; whereas the squamous cell carcinoma components were strongly positive for p40 but negative for CK7. The patient underwent postoperative chemotherapy and immunotherapy, and was followed up for 12 months, the patient’s health status was fairly good, with no recurrence or metastasis.