Patients with immunodeficiency disorders, including children infected with HIV type 1, are at increased risk to develop a malignancy. Although the exact incidence is not clear, an excess of non-Hodgkin's lymphomas, soft tissue tumors, and, in the case of adolescent girls, cervical carcinomas, has been reported in HIV-infected children. Kaposi's sarcoma is rare in children as compared with HIV-infected adults. To understand the pathogenesis of these disorders, one must take into account the multiple interactions between the immunodeficient host, the cytokine dysregulations, and the concurrent infection with many, potentially oncogenic, viruses. Treatment is often complicated by multiple HIV-associated organ dysfunctions as well as drug interactions and infectious complications secondary to severe immunosuppression. Nonetheless, preliminary results with dose-intensive short-duration chemotherapeutic regimens have been encouraging, and HIV-infected children who develop cancer are likely to benefit from antineoplastic therapy and supportive care.