We report a case of dermatomyositis (DM) and hemophagocytic lymphohistiocytosis (HLH) complicated by central nervous system (CNS) lesions and review eight literature cases of DM and HLH. A 17-year-old woman, admitted to our hospital because of severe muscle weakness and high fever, was diagnosed with DM based on elevated serum levels of muscle enzymes and a typical skin rash. Pancytopenia, high serum ferritin and soluble interleukin (IL)-2 receptor, and hepatosplenomegaly were also noted. Bone-marrow examination was negative for hemophagocytosis. Steroid therapy combined with immunoglobulin i.v. was ineffective against the DM, pancytopenia, hepatic dysfunction, and hyperferritinemia. On the 27th hospital day, seizures and acute respiratory failure occurred. In the course of improving muscle enzyme levels after starting adjunctive treatment with cyclosporine, the patient suffered disturbed consciousness, dyskinesia, and tremor. Brain magnetic resonance imaging (MRI) revealed T2 hyperintense lesions in the pons. Additional cyclophosphamide pulse therapy successfully decreased serum ferritin. Unfortunately, the diffuse alveolar damage (DAD) confirmed by biopsy progressed and the patient died. Autopsy findings revealed DAD throughout both lungs, HLH liver lesions, and a hemorrhagic necrotic lesion of the pons in the brain. Even when pathological examination yields no findings of hemophagocytosis, it is important to comprehensively and rapidly diagnose HLH based on the clinical picture. Because DM complicated by HLH may be associated with abnormal production of cytokines and systemic autoimmune responses, it may be necessary to immediately administer additional immunosuppressive therapy. We describe and discuss the extraordinary, severe form of DM in our patient, along with cases in the literature.