Acute myelofibrosis is a rare hematologic malignancy which usually follows a rapidly progressive, fatal course. A case of acute myelofibrosis and severe focal bone pain is described showing bone scan and plain radiograph findings. A biopsy of one of the abnormal bony areas revealed malignant cells, necrosis and fibrosis, and abnormal, exuberant new bone formation, which may account for what is seen on the radiographic and radionuclide studies. The etiology and optimal management of this rare and often rapidly fatal disease remain to be defined.