Eph receptors are cell surface protein tyrosine kinases that mediate cell-cell communication. The crystal structure of the full ectodomain of unliganded human EphA2 (eEphA2) reveals that it forms linear arrays of staggered, parallel receptors, whereas that of eEphA2 in complex with ephrinA5 forms a more elaborate assembly with interfaces that are crucial for localization at cell-cell contacts and for activation-dependent degradation.