Failed stereotactic biopsy is one in which a definitive histological or microbiological diagnosis is not achieved based on the tissue obtained. Of 518 consecutive CT-guided stereotactic biopsies of intra-axial mass lesions, 42 (8.1%) cases were failed biopsies. Inflammatory changes were seen in 10 cases (24%); gliosis was seen in 11 cases (26%); 9 cases (21%) yielded necrotic specimens; normal brain was retrieved in 7 cases (17%); blood/hemorrhagic brain was seen in 3 cases and in 2 cases, no tissue could be obtained. Variables that significantly influenced the diagnostic success included the immune status (HIV positive; p < 0.001). The complication rate in the failed biopsy group was significantly higher. The subsequent management and outcome of patients who suffered a failed stereotactic biopsy are discussed.