E3b1 is an Eps8 binding protein that transduces signal from Ras to Rac and regulates cell growth. In view of role of E3b1 as a cell growth regulatory signaling protein in the tumorigenesis of human tissues. The expression of E3b1 in human stomach and esophageal cancerous tissues and also in non-cancerous tissues was analyzed by western blotting technique. P65E3b1, P68E3b1 isoforms were found to be expressed in normal tissues and P72E3b1 isoform was found to be expressed in some normal tisssues whereas, P65E3b1and P68E3b1 isoforms were not found to be expressed in some stomach and esophageal cancers even P72E3b1 isoform was not found expressed in some stomach cancers. During this investigation, The general conclusion drawn is that the expression of P65E3b1, P68E3b1 and P72E3b1 in squamous cell carcinoma and adenocarcinoma is down regulated. Overall, the investigation led to the fact that E3b1 was related to human carcinogenesis & the expression level of E3b1 could be considered as a useful diagnostic marker for carcinogenesis.