OBJECTIVES: To report a patient with acute posterior multifocal placoid pigment epitheliopathy (APMPPE) who developed a thalamic infarction and to discuss this unusual presentation. DESIGN: Interventional case report and literature review. METHODS: A 23-year-old man with APMPPE presented with acute confusion and memory loss. He underwent complete ophthalmologic and neurologic examination, with neuroimaging including magnetic resonance angiography (MRA). MAIN OUTCOME MEASURES: Clinical course and angiographic findings. RESULTS: Magnetic resonance imaging (MRI) showed a left posteromedial thalamic infarction, with a corresponding filling defect of the left posterior communicating artery demonstrated by MRA. The patient underwent further treatment with intravenous corticosteroids followed by continued oral therapy with taper over several weeks. CONCLUSION: Although the association of APMPPE and cerebral vasculitis has been described, this patient is unique due to the subtle clinical presentation and anatomic location. This case emphasizes the importance of appropriate counseling of patients with APMPPE, as well as prompt recognition of clinical symptoms to enable timely intervention and treatment.