Penicilliosis marneffei, which is caused by the opportunistic fungus Penicillium marneffei, is one of the troublesome infections in patients infected with human immunodeficiency virus (HIV) in southeast Asia. We report an HIV-positive patient with acute disseminated penicilliosis marneffei that manifested as hemophagocytic syndrome. Numerous nucleated erythrocytes were also found in peripheral blood of the affected patient. Bone marrow aspirate histopathologically showed hemophagocytosis and abundant P. marneffei. The hemophagocytic syndrome and peripheral nucleated erythrocytes improved after therapy with amphotericin B. Our report underscores the importance of recognition of this peculiar phenomenon in penicilliosis marneffei. This awareness may alert clinicians to potential penicilliosis marneffei in HIV-positive patients, therefore making early diagnosis and timely effective treatment of the infectious disease possible.