Wider use of highly active antiretroviral treatment (HAART) for human immunodeficiency virus-1 (HIV-1)-infected patients has significantly altered the pattern of acquired immunodeficiency syndrome (AIDS)-related clinical signs and symptoms and has revolutionized the therapeutic modalities for these patients. Immune reconstitution inflammatory syndrome (IRIS) is a paradox of clinical worsening of opportunistic infections in the context of response to HAART and immunological recovery. Here we present a case of oral IRIS-related Kaposi sarcoma (KS) that appeared in an advanced HIV-1-infected patient introduced to HAART and was treated by surgical removal and antiretroviral therapy.