Thymic involvement is an important feature of human immunodeficiency virus-related disease in the pediatric population. The most common lesions are thymic involution or atrophy, thymitis (thymic lymphoid hyperplasia), and dysinvolution with loss of Hassall's corpuscles. We report a case of an unusual form of thymic enlargement in a human immunodeficiency virus-infected boy. In addition to lymphoid hyperplasia similar to that associated with human immunodeficiency virus infection in lymph nodes and other sites, the thymus was characterized by multilocular cysts with squamous epithelial lining (multilocular cystic lesion of the thymus).