Several rare histological variants of ependymoma have been described. The authors report on a patient in whom cervical spinal cord astrocytoma was originally diagnosed after evaluation of a limited biopsy specimen. More abundant tissue obtained during gross-total resection included areas of well-differentiated ependymoma. The histological features of the tumor were extremely unusual, with a major component of pleomorphic giant cells. Its histological, immunohistochemical, and electron microscopic features, however, were consistent with ependymoma. Only two cases of terminal filum and two of supratentorial giant cell variant of ependymoma have been reported. To the authors' knowledge, this represents the first case of giant cell ependymoma of the spinal cord. The clinical significance is the potential for misdiagnosis with anaplastic (gemistocytic) astrocytoma, especially in cases in whom limited biopsy samples have been obtained.