Most patients treated for single or multiple brain metastases die from progression of extracranial tumor activity. This makes it uncertain whether the combination of neurosurgery and radiotherapy for treatment of single brain metastasis will lead to better results than less invasive treatment with radiotherapy alone. The effect of neurosurgical excision plus radiotherapy was compared with radiotherapy alone in a prospectively randomized trial with 63 evaluable patients with systemic cancer and a radiological diagnosis of single brain metastasis. Radiotherapy was given to the whole brain by a novel scheme of 2 fractions per day of each 2 Gy for a total of 40 Gy. Before randomization, patients were stratified by site (lung cancer vs nonlung cancer) and status of extracranial disease (progressive vs stable). Survival as such and functionally independent survival (FIS; defined as World Health Organization performance status 5 1 and neurological function 5 1) were compared between both treatment arms. The combined treatment compared with radiotherapy alone led to a longer survival ( p = 0.04) and a longer FIS ( p = 0.06). This was most pronounced in patients with stable extracranial disease (median survival, 12 vs 7 mo; median FIS, 9 vs 4 mo). Patients with progressive extracranial cancer had a median overall survival of 5 months and a FIS of 2.5 months irrespective of given treatment. Improvement in functional status occurred more rapidly and for longer periods of time after neurosurgical excision and radiotherapy than after radiotherapy alone. Patients older than 60 years had a hazard ratio of dying of 2.74 ( p = 0.001) compared with younger patients, but in both age groups the combined treatment did better than radiotherapy alone. We conclude that patients with single brain metastasis and stable extracranial tumor activity should be treated with surgical excision and radiotherapy. For patients with progressive extracranial disease during the previous 3 months, radiotherapy alone appears to be sufficient. After treatment of single brain metastasis, patients remain functionally independent until a few months before death.