The relationship between Epstein Barr Virus (EBV) and the human host is commonly benign, whereas the development of malignancy is most likely due to imbalance between the virus and host's immune system. The aim of this study was to analyze the association of EBV with pediatric lymphomas in human immunodeficiency virus (HIV) patients. Four consecutive patients with a histological and clinical diagnosis of lymphomas among 351 pediatric HIV-infected children prospectively followed up at our hospital since 1991 were studied. The cases included one diffuse fibrosis lymphocyte depletion subtype Hodgkin's lymphoma, 2 Burkitt's lymphomas, and one primary diffuse large B-cell lymphoma of the central nervous system. We assessed EBV presence by LMP-1 protein labeling by immunohistochemistry and in situ hybridization for EBERs in formalin-fixed and paraffin-embedded biopsies from all four cases. All HIV-associated lymphomas studied were found to be associated with EBV. The lymphoproliferative action of EBV may induce oncogenesis by increasing the probability of genetic alterations and/or by expanding an already malignant clone. As an oncogenic protein, LMP-1 expression by tumor cells supports the involvement of EBV in disease pathogenesis.