A 48-year-old previously healthy man presented with headache, fever, and altered mental status. Brain MRI revealed >50 enhancing lesions across cortical, subcortical, and cerebellar regions. Echocardiography demonstrated a mitral valve mass initially interpreted as vegetation. Despite six weeks of empiric intravenous antibiotics and subsequent oral therapy, residual active lesions persisted. Surgical excision identified a cardiac myxoma rather than endocarditic vegetation. All blood cultures remained negative. Following resection and prolonged antibiotics, brain MRI demonstrated complete resolution. Neurocognitive testing improved to Montreal Cognitive Assessment score 26 at follow-up.