Abstract: A case of myelofibrosis secondary to systemic mastocytosis of ¹⁸F-FDG PET/CT imaging was reported. The characteristics of the disease were analyzed on the basis of clinical symptoms, laboratory examinations, imaging examinations, and bone trephine. The understanding of myelofibrosis and mastocytosis was deepened by literature review. Secondary myelofibrosis has numerous causes, one of which is mastocytosis. Mastocytosis is a blood system disease characterized by abnormal proliferation of mast cells in multiple tissues and organs. The histamine secreted by mast cells plays an important role in osteosclerosis. Lymphadenopathy characterized by enlarged liver and spleen is due to mast cell infiltration and extramedullary hematopoiesis. Symptoms of patients are also closely related to the chemical mediators secreted by mast cells.