ObjectiveTo explore the feasibility， safety and effectiveness of endoscopic submucosal dissection (ESD) in the treatment of the synchronous multiple early cancer or precancerous lesions in esophageal and stomach. MethodsA retrospective study was conducted on the data of 5 patients with synchronous multiple early cancer or precancerous lesions in esophageal and stomach who were treated by ESD in Endoscopy Center of Zhongshan Hospital from January 2008 to December 2013. The characteristics of lesions， and results of therapy and follow-up were analyzed. ResultsAll 5 patients were male with mean age of 67.8±13.1 years. The mean size of esophageal lesions was 2.1±0.9 cm with 1 lesion located in the upper esophagus and 4 in the middle. The mean size of gastric lesions was 2.5±1.5 cm with 2 lesions in the antrum， 2 in the gastric angle and 1 in cardia. Lesions in 4 cases were removed at the same time and 1 at different times. All lesions achieved complete resection. Postoperative pathologicalresults showed that there were 2 cases of esophageal precancerous lesions with gastric precancerous lesions， 2 cases of esophageal precancerous lesions with early gastric cancer， and 1 case of early esophageal cancer with early gastric cancer. The 5 patients with 10 lesions all achieved curative resection. Postoperative esophageal stricture occurred in 1 case， which was improved after dilation. Median follow-up time was 72 months， when 3 patients survived and 2 patients died. However， the cause of death was not associated with the treatment. ConclusionESD is a minimally invasive endoscopic method for treating synchronous multiple primary early cancers in esophagus and stomach.