Solitary eosinophilic granuloma of the skull is a rare lesion, the natural history of which has not been defined completely. By a retrospective chart review, 26 patients were identified as having a solitary eosinophilic granuloma of the skull at first presentation to our institution between 1946 and 1982. Characteristically, the patient noted an enlarging, tender skull mass during the several weeks to several months before the initial assessment. Laboratory findings were normal except for 1 case of eosinophilia. Radiographically, the abnormality consisted of a punched-out, well defined, lytic lesion most commonly seen in the parietal or frontal bone. Whole body bone scans or bone surveys were used to rule out further lesions. The definitive diagnosis was made by histological examination, which showed the characteristic histiocytes, eosinophils, and multinucleated cells of eosinophilic granuloma. The usual treatment consisted of a craniectomy or curettage perhaps followed by local, moderate dose radiation therapy. The follow-up period ranged from 1 month to 25 years and averaged 8 years; in that time, 8 patients (31%) developed additional lesions. Of these 8 patients, only 3 were older than 3 years at the time of the first recurrence. Based on a review of our own patients and those reported in the literature, we stress that a solitary eosinophilic granuloma of the skull may foreshadow future disease elsewhere and is not an easily dimissed local disease, especially in children. After the initial treatment, we recommend careful long term follow-up and treatment of additional lesions with radiation therapy.