These findings taken together with the established role of EPHB receptors in colorectal cancer, prompted us to hypothesize that germline EPHB2 mutations may account for at least a fraction of the genetic alterations underlying the unexplained portion of hereditary colorectal cancer, and may represent a new cancer syndrome causing genetic predisposition to colorectal and prostate cancer. The gene discussed is EPHB2; the disease is familial colorectal cancer.