Analysis of recent reports has suggested that cavernous malformations (CMs) of the brain may have an acquired pathogenesis and a dynamic pathophysiological composition, with documented appearance of new lesions in familial cases and following radiotherapy. The authors report the first case of demonstrated de novo formation of an intramedullary CM following spinal radiation therapy. A 17 year-old boy presented with diabetes insipidus and delayed puberty. Evaluation of endocrine levels revealed hypopituitarism, and magnetic resonance (MR) imaging demonstrated an infundibular mass. The patient underwent a pterional craniotomy and removal of an infundibular germinoma. The MR image of the spine demonstrated normal results. The patient received craniospinal radiation therapy and did well. He presented 5 years later with acute onset of back pain, lower-extremity weakness and numbness, and difficulty with urination. An MR image obtained of the spine revealed an intramedullary T-7 lesion; its signal characteristics were consistent with a CM. The patient was initially managed conservatively but developed progressive myelopathy and partial Brown-Séquard syndrome. Although he received high-dose steroids and bed rest, his symptoms worsened. He underwent a costotransversectomy and excision of a hemorrhagic vascular lesion via an anterolateral myelotomy. Pathological examination confirmed features of a CM. The patient has done well and was walking without assistance within 4 weeks of surgery. De novo genesis of CMs may be associated with prior radiation therapy to the spinal cord.