Non-neoplastic hemophagocytic syndrome (HPS), also called virus-associated hemophagocytic syndrome (VAHS), has been thought to be a distinct clinical entity. A spontaneous recovery is common, but the prognosis of Epstein-Barr virus (EBV)-associated VAHS is poor. However, the role of EBV has yet to be clearly elucidated. A retrospective study of the bone marrow of 30 cases, in which the diagnosis of non-neoplastic VAHS was clinicopathologically confirmed, was performed. We were unable to histologically confirm the presence of neoplastic lesions, especially lymphoma cell infiltration. Ten of the patients were children (aged less than 15 years) and young adults (aged under 20 years; median age, 10 years). Twenty patients were adults (aged over 21 years; median age, 48 years). Twelve of these patients died, while 18 showed a spontaneous recovery. We performed immunological staining and in situ hybridization (ISH) for EBV. To clarify the presence of apoptosis, an in situ apoptosis detection (tunnel) method was used. In situ hydridization showed an EBV-presence in 16 of the 30 patients. In addition, the EBV-presence was confined in the lymphocytes, especially T lymphocytes in double stainings. The number of EBV-infected cells varied; however, the EBV presence was associated with ages. Nine of the 10 children and young adults showed an EBV-presence, while EBV was detected in seven of the 20 adults. Especially in 10 patients aged over 49 years, no EBV was detected. According to the in situ apoptosis detection, apoptotic cells were increased in number and considered to be lymphoid cells, but not myeloid or histiocytic cells. Some apoptotic cells were phagocyted with histiocytes. Histologically, apoptosis may be one of the factors that induced phagocytosis.