Oral ulcers observed during the course of HIV infection may be very severe. Such manifestations may interfere with oral functions and alter the patients' quality of life. It is important to stress that when HIV-infected individuals present with ulcerative lesions of the oral cavity, neoplastic processes and rare infections must be included in the differential diagnosis. Nontumefactive oral ulcers in HIV-positive patients may be a source of diagnostic difficulties because of the diverse array of underlying pathologic entities and multiplicity of etiologic agents. Biopsy should always be performed on long-standing ulcers, since either infection or a neoplastic process may be present. In the absence of infection or neoplasm, such lesions are then designated ulcers not otherwise specified.