The pathological findings in a retrospective review of 100 consecutive intracranial stereotactic biopsies are presented. Definite diagnosis could be established in the majority (89) of cases and included 85 neoplasms (69 primary cerebral tumors, 10 non-Hodgkin's lymphomas and 6 metastases) and 4 non-neoplastic processes. In the remaining 11 samples the findings were non-diagnostic; 2 consisted of normal glial tissue, while the remainder variously showed changes of necrosis, hematoma, histiocytic reaction or astrocytic proliferations of uncertain nature. Verification of the stereotactic diagnosis by examination of lesional tissue obtained at subsequent craniotomy or postmortem was possible in 7 of 10 cases. Two broad categories of diagnostic difficulty were identified in interpreting stereotactic biopsies: (1) accurate tumor typing and grading, and (2) the distinction between reactive and neoplastic astrocytic proliferations. Two essential components in the diagnostic process are: (1) careful correlation with the clinical and radiological findings; and (2) use of intraoperative smear and/or frozen section preparations to confirm specimen adequacy. By adhering to these principles accurate intraoperative diagnosis can usually be established, particularly for high grade astrocytoma, lymphoma and metastasis. Tumor typing is aided by the use of immunohistochemistry and ultrastructural examination and the examination of serial sections is of value in grading.