EPHB2 is a member of the Eph receptor tyrosine kinase family and a direct transcriptional target of beta-catenin/TCF. EPHB2 plays an important role in maintaining the correct positioning of the proliferative compartment in the crypt-villous axis. A loss of EPHB2 expression has been observed in human tumors, particularly in colonic adenomas and carcinomas. A search was made for mutations at the A9 tract in exon 17, an allelic loss at the EPHB2 gene locus, and promoter hypermethylation of the EPHB2 gene in 81 sporadic gastric cancers in order to determine if genetic or epigenetic alterations of the EPHB2 gene are involved in the development and/or progression of gastric cancer. Unexpectedly, no frameshift mutation was found and there was a low frequency (20.8%) of allelic loss. In addition, promoter hypermethylation was detected in only one gastric cancer tissue sample. Therefore, genetic or epigenetic alterations of the EPHB2 gene might be an uncommon event in the development or progression of gastric cancers.