Histiocytic sarcoma is a rare malignant neoplasm of the lympho-hematopoietic system that usually occurs in the skin, lymph nodes and intestinal tract. We present a 36-year-old woman with a rare histiocytic sarcoma with isolated central nervous system (CNS) involvement of multifocal circumscribed lesions. Biopsy of the brain lesions showed diffuse proliferation of pleomorphic histiocytes that were immunopositive for CD45, CD68 and CD163. Various cytokeratins and markers of lymphoma, melanoma, germ cell tumours and primary CNS tumours were negative. Examination of bone marrow trephine and a whole-body positron emission tomography scan showed no evidence of involvement of any other organ systems, thus establishing the primary nature of the lesion. The neoplastic cells uniquely showed eosinophilic globules within the cytoplasm, which were positive for CD68. These globules were shown by electron microscopy to be collections of lysosomes. A thorough discussion of the differential diagnosis and literature review is included.