The aim of the study was to identify the frequency of asymptomatic brain metastases detected by computed tomography (CT) scans in patients with metastatic cutaneous melanoma referred to first-line systemic treatment. Between 1995 and 2009, 697 Danish patients were screened with a contrast-enhanced CT scan of the brain before the start of interleukin-2 (IL-2)-based immunotherapy. Among the 697 patients, 80 had asymptomatic brain metastases (12%). Patients' characteristics did not differ significantly between groups with and without brain metastases. Patients received systemic treatment (IL-2-based or cytotoxic chemotherapy), local treatment (stereotactic radiotherapy, whole-brain radiotherapy or surgery), or best supportive care only. The survival was significantly shorter for patients with asymptomatic brain metastases compared with patients without brain metastases (P<0.0001). The median survival was 4.5 versus 9.2 months; 1-year survival was 12.5 versus 38.4% for patients with or without asymptomatic brain metastases, respectively. We conclude that 12% of patients with metastatic cutaneous melanoma who qualified clinically for IL-2 treatment had asymptomatic brain metastases, detected by CT scans with contrast. Proper staging of metastatic cutaneous melanoma including contrast-enhanced CT of neck, thorax, and abdomen and contrast-enhanced MRI of the brain is mandatory, as systemic treatment options with comparable safety and efficacy in patients with and without brain metastases have emerged.