To identify predictive findings in children with nontraumatic acquired cavernous sinus lesions, a retrospective study of the clinical course of 4 of our own patients and 17 more children found in an extensive literature search was performed. Mean age was 8.7 years. Malignancy was found in 11 of 21 children (6 female, 15 male). Of these 21 children, 9 were cured, 8 are either in remission or their course is unknown, and 4 died. Eight of the nine cured patients were diagnosed as having had Tolosa-Hunt syndrome. Of the four deceased children, three had a very short course (1 to 4 months) and were diagnosed with malignant lymphoma (n = 2) and rhabdomyosarcoma (n = 1). One patient died from a brain tumor other than the initially diagnosed T-cell lymphoma in the cavernous sinus after a follow-up of 8 years. MRI should be the preferred imaging technique—even if it is not conclusive in many cases—and every possible diagnostic effort should be made before using corticosteroids. No clinical or radiological signs other than rapid deterioration seem to be predictable of a malignant cavernous sinus lesion with poor outcome. Thus, close follow-up is recommended in children with signs and symptoms indicative of an acquired lesion in the cavernous sinus.