A 60-year-old female presented with a history of progressive shortness of breath, fever, and weight loss of 55 pounds. The work-up consisting of computerized axial tomography (CT) scan of thorax and abdomen, mediastinoscopy, and bilateral bone marrow aspiration and biopsy revealed a large-cell or histiocytic lymphoma involving bone marrow with myelofibrosis. Further immunologic and ultrastructural investigation confirmed the true histiocytic origin of the tumor. The patient was treated with 12 courses of intravenous cyclophosphamide, onconvin, doxorubicin, and prednisone and achieved a complete remission with disappearance of clinical symptoms, normal CT scan of thorax and abdomen, and normal bone marrow with disappearance of myelofibrosis from the same site as the previous bone marrow test. At present the patient is in complete remission. We present this case because of the previously unreported association between histiocytic lymphoma and myelofibrosis, and the unusually good response to chemotherapy and the disappearance of fibrosis from the marrow.