Patients infected with HIV experience a spectrum of lymphoproliferative disorders, including generalized reactive lymphadenopathy to atypical lymphoproliferative lesions and lymphomas. Polymorphic B-cell lymphoproliferative disorders are rare and not well documented. We studied lung lesions from two children infected with HIV: an atypical polymorphic B-cell hyperplasia in a 14-year-old boy and a malignant polymorphic B-cell lymphoma in a 21-month-old girl. Morphologically, both lung lesions revealed similar polymorphic lymphoid infiltrations with numerous mitoses in case 1 and extensive necrosis and architectural distortion in case 2. Immunophenotypic examination showed no predominance of κ or λ light chain in case 1 and a predominance of κ light chain in case 2. Genotypic analysis demonstrated an absence of immunoglobulin and T-cell receptor gene rearrangements in case 1 and the presence of biallelic immunoglobulin heavy chain rearrangement and a single clonal Epstein-Barr virus (EBV) in case 2. The clinical course was indolent in case 1 and aggressive in case 2. The clinicopathologic features were similar to those of posttransplantation lymphoproliferative disorders suggesting that these lung lesions might represent an immunosuppression-related spectrum of benign to malignant diseases. EBV infection may play a role in the pathogenesis of these lesions. This study highlights the importance of the molecular characterization of AIDS-associated lymphoproliferative disorders in children in establishing a definitive diagnosis.