Kaposi sarcoma inflammatory cytokine syndrome is a rare and fatal malignancy that is challenging to treat. The syndrome appears in individuals who are both human immunodeficiency virus and human herpesvirus 8 positive. The diagnosis of disease is challenging because its presentation mimics sepsis and it has a high mortality rate. A bone marrow biopsy is necessary for definitive diagnosis. This case report discusses a 40-year-old human immunodeficiency virus infection-positive African American male who presented to the emergency department with a chief complaint of left hallux pain in January 2018 after a trip to a nail salon in December 2017. Radiographic and magnetic resonance images suggested osteomyelitis of the distal phalanx, and Gram stain of bone showed gram-negative rods. The patient was started on antibiotic therapy for presumed osteomyelitis. As the patient’s status deteriorated, a partial hallux amputation was then performed. Intraoperative specimens were negative for bacterial involvement, but pathology was positive for Kaposi sarcoma. During a 7-month progression, the patient’s hematologic and overall status continued to decline. Despite diagnostic and treatment guidelines being followed, the patient died from this illness in July 2018. This case is interesting because of the atypical presentation of Kaposi sarcoma and highlights the rapid progression of the disease.Copyright © 2019 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.