Leiomyosarcoma is a rare Epstein-Barr virus (EBV)-related complication of solid-organ transplantation. We report the case of a 19-year-old woman with cystic fibrosis who presented with protracted headaches 15 months after an EBV-mismatched bilateral sequential lung transplant. A parasagittal lesion was found on cranial magnetic resonance imaging; surgical resection revealed a leiomyosarcoma. We discuss treatment options of what is, to our knowledge, the first described case of a cranial leiomyosarcoma in a lung transplant recipient.