EPS8 protein has been known to be involved in the signaling pathway of different cancers, and protein E3B1 is considered to be a downstream target for EPS8. By participating in the formation of various macromolecular complexes, E3B1 has been found to mediate a number of signal pathways related to cancer cell proliferation. We carried out expression analysis studies of EPS8 in esophageal, stomach and lung carcinomas, and observed increased expression of the protein in esophageal and stomach cancers, whereas, the observed expression of this protein in lung cancers was fairly equal. Likewise, the expression of E3B1 was studied in esophageal, breast, gastro-eophageal junction, stomach and colorectal cancers, and observed a consistent decrease in all these cancers except for breast cancers where no change in expression was observed. Our data supports a novel cancer-specific role of the two proteins in the mentioned cancers and suggest EPS8 and E3B1 could have a pivotal role in the progression of these cancers.