OBJECTIVE To quantitate features that distinguish the plain radiographic appearance of eosinophilic granuloma (EG) from other solitary lesions of bone. METHODS Seven hundred nine focal bone lesions, including 26 EGs, were analyzed according to demographic, anatomic, and plain radiographic features. Vector analysis of groups of features was performed to determine those that are most sensitive and specific for the appearance of EG in contrast to other lesions in the data base. RESULTS The radiographic appearance of EGs was most consistently that of a medullary based lytic lesion (100%) with geographic destruction (76.9%), lobular contour (73.1%), and well-defined edges (73.1%). Long bone lesions showed these features more frequently than EGs in other locations. Periosteal reaction was visible in all long bone lesions but in only one nonlong bone lesion (5.9%). Characterization of EG in long bones as a lytic, medullary-based metaphyseal or diaphyseal lesion with geographic destruction, lobular contours, periosteal reaction, no matrix, and no subarticular extension showed a sensitivity of 55.6% of EG and prevalence of 22.7%. The vector analysis-generated differential diagnoses include unicameral bone cyst, aneurysmal bone cyst, giant cell tumor, Brodie's abscess, enchondroma, chondrosarcoma, and malignant fibrous histiocytoma. CONCLUSIONS The radiographic appearance of EG is relatively nonspecific but, using vector analysis, can be better elucidated than in current textbook descriptions.