Treatment of HIV-infected individuals with highly active antiretroviral therapy (HAART) has resulted in an impressive reduction in the incidence of opportunistic infections (OIs). However, some patients develop paradoxical infections (de novo or flares of previously known OIs) shortly after the initiation of HAART, a phenomenon known as immune reconstitution inflammatory syndrome (IRIS). In addition to OIs developing in the setting of IRIS, more recently, non-Hodgkin lymphomas have also been reported to occur in this context. To our knowledge, this is the first case of pericardial large B-cell lymphoma reported in an HIV-infected individual shortly after the initiation of HAART. We review the literature on IRIS-associated lymphomas apropos to this case report.