Malignancies in children with HIV infection have not been as frequent as expected, but they still constitute a fertile area for clinical and basic research. Non-Hodgkin's lymphomas are the most frequent malignancies of children with AIDS and are curable diseases with standard chemotherapy. Leiomyomas and leiomyosarcomas have become the second leading cancer of children with HIV infection and are clearly associated with EBV infection. Treatment for these lesions has not been as successful as that for lymphomas. Other infrequent atypical lymphoproliferative lesions of these patients can often be categorized in the MALT group. Some of these are low-grade lymphomas, whereas others can progress to high grade. The diagnosis of Kaposi's sarcoma in children with AIDS should be carefully reviewed by pathologists experienced with these cases. The diagnosis of KS in children must be made with special care, because some other lesions of HIV-infected children (such as prominent vascularity in lymph nodes) can be confused with KS. Other tumors of these patients are rare and probably are no more frequent than would be expected in the normal population. Because malignancies in children with AIDS are rare, it is important that each one be studied completely with regard to type and incidence, risk factors, and biologic features. To this end, the Pediatric Oncology Group (POG) has established a national registry and treatment protocols. Patient information as well as fresh, frozen, and fixed specimen studies are coordinated through the POG Statistical Office in Gainesville, Florida (telephone, 904-392-5198; FAX, 904-392-8162). The collaborative efforts of all physicians treating children with AIDS and malignancies will be needed to advance our knowledge and efficacy in treating these diseases.