Several inflammatory, infectious, and neoplastic conditions in HIV-infected patients are distinctive or require a biopsy for diagnosis. Some differ subtly from similar conditions seen in noninfected patients. The exanthem of acute HIV infection cannot be diagnosed specifically on biopsy as its histologic appearance is similar to that of other viral exanthemata. A condition that closely resembles seborrheic dermatitis occurs in HIV-infected patients. Plasma cells, necrotic keratinocytes, and leukocytoclasis may be present, in contrast to findings in sporadic seborrheic dermatitis. Psoriasis and Reiter's disease also occur in HIV-infected patients and can be specifically diagnosed as such. The category "psoriasiform dermatitis of AIDS" thus seems to include several distinct entities and not to be a single disease. Bacillary angiomatosis is a treatable infection caused by a rickettsialike organism similar to Rochalimaea quintana, the agent of trench fever. Cutaneous lesions are characterized by lobules of capillaries with protuberant endothelial cells, neutrophils and their debris, and purplish-staining clumps of organisms, which can be demonstrated with silver stains or electron microscopy. An unusual reaction to atypical mycobacterial infection, in which spindle-shaped macrophages are seen, resembles histoid leprosy. Viral skin diseases that may challenge the dermatopathologist include unusual verrucous reactions to chronic varicella-zoster infection and flat warts caused by the human papillomavirus associated with epidermodysplasia verruciformis. Keratinocytes with foamy basophilic cytoplasm may be a marker for one of these viruses, human papillomavirus type 5. Neoplastic complications of HIV disease include Kaposi's sarcoma and mycosis fungoides. The earliest lesions of the patch stage of Kaposi's sarcoma show a slightly increased number of cells with small ovoid nuclei around preexistent structures, accompanied, in some cases, by sparse infiltrates of lymphocytes and plasma cells. Staining with antisera to type IV collagen may highlight the vascular spaces in these early lesions. Later lesions that resemble hemangiomas may also prove challenging and require level sections to demonstrate the presence of spindle cells and eosinophilic globules. Although HIV is cytotoxic to helper T cells, neoplastic proliferations of them may be seen in HIV-infected patients. These cases of mycosis fungoides do not seem to differ from sporadically occurring ones and occur in patients who seem not to be infected by HTLV-I.