We demonstrate that EphA5 is expressed in many human solid tumors, including aerodigestive tract tumors (non–small cell lung [NSCLC], head and neck, gastric, colon, and pancreatic cancers), genitourinary tract tumors (bladder and ovarian cancers), and most subsets of breast tumors (including triple-negative cancer). Here, EPHA5 is linked to familial pancreatic carcinoma.