Metastatic cancer to the brain has a poor prognosis. The focus of this work was to determine the incidence of long-term (≥2 y) survival for patients with brain metastases from different primary cancers and to identify prognostic variables associated with prolonged survival. A retrospective review of 740 patients with brain metastases treated over a 20 y period identified 51 that survived 2 or more years from the time of diagnosis of the brain metastasis. Prognostic variables that were examined included age, sex, histology, tumor number and location, and treatment. In the 51 patients, 35 (69%) had single lesions and 16 (31%) had multiple tumors. For all tumor types (740 patients), the actuarial survival rate was 8.1% at 2 y, 4.8% at 3 y, and 2.4% at 5 y. At 2 y, patients with ovarian carcinoma had the highest survival rate (23.9%) and patients with small cell lung cancer (SCLC) had the lowest survival rate (1.7%). At 5 y, survival rates were 7.8% for ovarian carcinoma, 2.9% for non-SCLC, 2.3% for melanoma and renal cell carcinoma, 1.3% for breast carcinoma and there were no survivors with SCLC, gastrointestinal, bladder, unknown primary, or prostate cancer. Age, sex, histology, location for single tumors, systemic chemotherapy, and stereotactic radiosurgery did not significantly influence survival. The presence of a single lesion (P=0.001, chi-square test), surgical resection (P=0.001), and WBRT (P=0.009) were favorable prognostic variables for extended survival. Multiple bilateral metastases was a poor prognostic indicator (P=0.001). Multivariate analysis showed younger age (P<0.05), single metastasis (P<0.0001), surgical resection (P<0.0001), whole brain radiation therapy (P<0.0001), and chemotherapy (P=0.0288) were associated with prolonged survival. 29 patients (57%) died of systemic disease progression, 9 (18%) died of central nervous system progression, and the cause of death was unknown in 3 (6%). Patients with a single non-SCLC, breast, melanoma, renal cell, and ovarian carcinoma brain metastasis have the best chance for long-term survival if treated with surgical resection and WBRT.