Granular cell astrocytoma (GCA) is an uncommon malignant glial tumour that is associated with a poor prognosis. GCA cells have some morphological and immunohistochemical similarities to macrophages. In this case, a small biopsy contained no typical astrocytoma and large rounded lesional cells were interpreted as negative for glial fibrillary acidic protein and S100 and positive for CD68, a commonly used marker for macrophages. A diagnosis of a histiocytosis was made. When the patient failed to respond to first and second line therapy, tumour resection was undertaken and the pathology then showed typical morphologic and immunohistochemical features of glioblastoma (astrocytoma World Health Organization grade IV).