Objective To analyze the clinicopathological features of histological mixed-type early gastric cancer and to compare the endoscopic pathological features of dominant proportions. Methods Clinical data of 43 patients with histological mixed-type early gastric cancer who underwent endoscopic submucosal dissection (ESD) at the Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2015 to December 2020 were retrospectively analyzed. The endoscopic characteristics, coincidence rate of preoperative diagnosis and postoperative pathology of the patients were analyzed. The endoscopic pathological findings of differentiation dominant group and undifferentiation dominant group were compared. Results Histological mixed-type early gastric cancer was more common in patients over 60 years old (55.81%, 24/43) , male (65.12%, 28/43), and Helicobacter pylori (HP) infection (69.77%, 30/43). Most lesions were found in atrophic background (79.07%, 34/43), and lower part of stomach (65.12%, 28/43). Redness or mixed redness was the main color (76.74%, 33/43), and 0-Ⅱc was the main type in lesion morphology (58.14%, 25/43). Characteristics of both differentiated and undifferentiated carcinoma could be observed under magnifying endoscopy. Only 16.28% (7/43) of the patients were diagnosed as having histological mixed-type carcinoma by biopsy. Postoperative pathology showed that there were 33 cases in differentiation dominant group and 10 cases in undifferentiation dominant group. There were 15 (34.88%) patients with deep submucosal infiltration, and 3 (6.98%) patients with positive lymphatic vessels. Differentiation dominant group had clearer demarcation line under endoscopy [78.79% (26/33) VS 4/10, χ2=7.753, P=0.012]. There was no significant difference between the two groups in gender, HP infection, background mucosa, lesion location, endoscopic morphology, lesion long diameter, color, or microscopic and microvascular manifestations under magnifying endoscopy (P>0.05). Tub2+por was the most common pathological type in differentiation dominant group (78.79%, 26/33), and sig+tub2 was the dominant combination in undifferentiation dominant group (6/10). Endoscopic diagnosis of differentiated primary carcinoma was highly sensitive (93.94%, 31/33), and highly specific for undifferentiated primary carcinoma (94.28%, 33/35). Conclusion Histological mixed-type early gastric cancer can be diagnosed qualitatively by endoscopy. It is difficult to accurately judge the differentiation advantage and the invasion depth before the operation, which is prone to postoperative pathological upgrading. Therefore, the indications should be strictly considered for ESD treatment for mixed-type early gastric cancer.