To investigate the clinical characteristics of patients with brain metastases as the initial manifestation of their systemic cancer in a Chinese population, a retrospective study of 254 such patients admitted to Huashan Hospital, Fudan University, Shanghai, China between January 1, 2003 and December 30, 2008 was performed. Data were collected to determine the features of this group (i.e., manifesting signs and symptoms, imaging studies, extracerebral metastases, primary tumor sites, initial diagnosis, and survival data). Common symptoms included headache and motor impairment. The distribution of brain metastases paralleled blood flow, and the majority of brain metastases were located in the cerebral hemispheres. Magnetic resonance imaging (MRI) was more sensitive than computed tomography (CT) for confirming presence of brain lesions. This distinct clinical entity exhibited high rates of misdiagnosis at initial presentation. Pathology varied, and adenocarcinomas were most commonly observed. Underlying primary tumors were identified in 84.2% of patients, most often located in lung (71.7%), followed by digestive tract. Chest CT had high yield. Sixty-two patients presented with silent extracerebral metastases at initial presentation. Median survival time was 15 months (95% confidence interval, 12.2–17.8 months). Survival rates for 1, 2, and 5 years were 59.2%, 23.2%, and 15.1%, respectively. Contrast-enhanced MRI had high yield for detection of brain metastases. Adenocarcinoma was the most common histologic type. Given the high frequency of primary lung tumors and the sensitivity of chest CT, chest CT should be a part of the initial screen of primary site with brain metastases as the initial manifestation. Metastatic dissemination of malignancy to the brain as the initial manifestation is generally associated with dismal prognosis, with the exception of a minority who experience long survival.