The majority of computer tomography stereotactic biopsy lesions enhance after administration of intravenous contrast, whereas patients with nonenhancing lesions are often followed conservatively or undergo craniotomies. There are few studies showing the effectiveness of stereotactic biopsies of nonenhancing cerebral lesions. Stereotactic biopsies were performed on 19 patients with lesions that did not enhance on CT after intravenous contrast. Pathological diagnoses were made in 90% (17/19) of patients. Four HIV-positive patients had progressive multifocal leukoencephalopathy, 11 patients had gliomas (4 astrocytomas, 6 anaplastic astrocytomas, and 1 ganglioma), 1 had multiple sclerosis, and 1 had herpes encephalitis. In 2 patients multiple biopsies revealed only gliosis. There was no morbidity or mortality. Stereotactic biopsies for nonenhancing brain lesions have a high diagnostic yield and can favorably alter the treatment course.