The Eph gene family has important roles in the developmental processes and may also be involved in the initiation, progression, and metastasis of certain types of cancers. In the present study, quantitative real-time reverse-transcriptase PCR was performed to detect the expression of EphA1 transcript in 5 colon cancer cell lines and 75 colorectal carcinomas. Immunohistochemical staining was used to check the expression of EphA1 protein in 20 colorectal adenomas and in 111 colorectal carcinomas specimens. EphA1 protein expression was not completely consistent with transcript expression. EphA1 protein was expressed in all adenomas and reduced in 54% colorectal cancers. Reduced expression of EphA1 protein occurred more often in male patients (P=0.028) and in patients with poor differentiation (P=0.027), greater depth of wall invasion (P=0.003), lymph node metastasis (P=0.034), and advanced tumor stage (P=0.003). Patients with reduced EphA1 expression had a poor overall survival (P=0.059). Reduced EphA1 expression in patients over 55 years or with rectal cancers and sigmoid colon cancers is associated with a poor overall survival (P=0.034 and 0.015, respectively). Our data indicate that the EphA1 may play different roles during the different stages of colorectal carcinoma progression.odern Pathology (2009) 22, 151-160; doi:10.1038/modpathol.2008.188; published online 14 November 2008.