A 34-year old white man with a 3-year history of eczema presented with a 3-week history of fevers, chills, and a rapidly enlarging 5-cm left thigh mass. His eczema had evolved into erythroderma with hyperkeratotic palms and soles. The mass was excised, and histopathologic analysis showed a dense infiltrate of large CD8+ anaplastic tumor cells extending from the epidermis to the panniculus with Pautrier microabscesses (Figure 1 and Figure 2). An oligoclonal T-cell gene rearrangement was detected by polymerase chain reaction (PCR). A remote skin biopsy finding was consistent with mycosis fungoides (MF) and/or cutaneous T-cell lymphoma (CTCL) and demonstrated a positive monoclonal T-cell receptor gene rearrangement by PCR. Blood flow cytometry showed an inverted CD4/CD8 ratio of 0.1. Antibody testing for human immunodeficiency virus (HIV) and human T-cell lymphotrophic virus 1 and 2 revealed that the patient was HIV positive. The CD4 cell count was 150 cells/mL, and viral load was greater than 100 000 copies/mL. The patient started highly active antiretroviral therapy (HAART) of fixed-dose zidovudine, zidovudine, lamivudine, and abacavir plus efavirenz to decrease his viral load prior to initiating lymphoma-specific systemic therapy. After 2 months of HAART and treatment with topical 0.1% triamcinolone ointment, the patient’s viral load decreased to 111 copies/mL, his erythroderma had improved, and his pruritis, fever, and chills had resolved. By January 2004, his erythroderma had resolved, his CD4+ T-cell count had increased to 507 cells/mL, and his viral load was less than 75 copies/mL.