BACKGROUND Kaposi's sarcoma (KS) is a common condition in patients with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). In these patients, the occurrence of KS is reduced by treatment with highly active antiretroviral therapy (HAART). Fatal and disseminated KS is presented in two patients with HIV/AIDS. CASE REPORT A 25-year-old man and a 30-year-old man with HIV/AIDS presented with KS affecting the skin, oral cavity, gastrointestinal tract, liver, lungs, kidneys, adrenal glands, and bone. Both patients had a rapidly deteriorating clinical course associated with a low CD4 count and developed respiratory failure and death. CONCLUSIONS Fatal disseminated KS is associated with severe immunosuppression due to with a low CD4 count. The presentation of these two cases highlights the potentially aggressive clinical course of KS in patients with HIV/AIDS and reinforces the need for early diagnosis and rapid treatment with HAART.