Stroke in children is relatively uncommon. We describe an 8-year-old boy diagnosed with primary eosinophilic granuloma (EG) of the frontal bone. After excision of the EG, the postoperative course was eventful. The patient had an acute right middle cerebral artery (MCA) infarct and had been comatose with a diminished Glasgow Coma Scale (GCS) score of 5. Urgent decompressive hemicraniectomy with duraplasty was performed. The postoperative course after the second operation was uneventful. Hematological tests revealed a diagnosis of factor V Leiden. The patient was discharged with left hemiparesis and GCS of 15. To the best of our knowledge, no such clinical picture of MCA infarction after EG excision has been described before. Neurosurgeons should be aware of inherited thrombophilias, such as factor V Leiden, if the postoperative clinical course worsens because of cerebral artery thrombosis. Also, decompressive hemicraniectomy could be life saving and should be performed urgently without any hesitation.