To ascertain the range of neurological problems in patients with systemic cancer, we prospectively evaluated neurological symptoms, neurological diagnoses, and primary tumors in all patients with a history of systemic cancer examined by the Department of Neurology at the Memorial Sloan-Kettering Cancer Center, from Jul 1, 1990, to Dec 31, 1990. Of the 815 patients seen for neurological symptoms, less than half (45.2%) had metastatic involvement of the nervous system. The three most common symptoms were back pain (18.2%), altered mental status (17.1%), and headache (15.4%). The most common neurological diagnosis was brain metastasis (15.9%), followed by metabolic encephalopathy (10.2%), pain associated with bone metastases only (9.9%), and epidural extension or metastasis of tumor (8.4%). Of 133 patients with undiagnosed back or neck pain, 44 (33%) had epidural extension or metastases from tumor and 40 (30%) had pain associated with vertebral metastases only. In 15 (11%) the cause for the back pain was unrelated to metastatic disease. Of 132 patients seen on initial consultation for altered mental status, metabolic encephalopathy was the major neurological diagnosis (80; 61%); 20 (15%) had intracranial metastases. Of 97 patients with undiagnosed headache, 59 (61%) had a nonstructural cause. Fifty-three of these patients had either migraine, tension headache, or headache related to systemic illness (e.g., fever, sepsis). These results indicate that even in patients with systemic cancer, a group particularly prone to developing neurological disease that can be diagnosed radiologically, the role of clinicians remains important in helping distinguish noncancer-related and nonmetastatic neurological problems.