Background <p>Fatal familial insomnia (FFI) has an insidious onset and the typical clinical presentation includes sleep disorders and autonomic dysfunction, making early diagnosis challenging. We present the radiological changes observed in ¹⁸F-FDG PET/MRI from onset to advanced stages of FFI.</p> Case presentation <p>A 42-year-old woman underwent ¹⁸F-FDG PET/MRI due to sleep disorders and autonomic dysfunction. ¹⁸F-FDG PET/MRI showed decreased glucose metabolism in the bilateral frontal cortex, head of the caudate nucleus, and thalamus, whereas no abnormalities were detected on T1WI, FLAIR, and DWI. Three and a half months later, the patient’s symptoms worsened, and ¹⁸F-FDG PET/MRI showed a further decline in glucose metabolism and involvement of the bilateral parietal cortex and putamen. Finally, genetic testing confirmed the diagnosis of FFI.</p> Conclusions <p>¹⁸F-FDG PET/MRI may provide valuable supportive information in cases of suspected FFI, particularly by revealing characteristic glucose metabolic patterns that complement clinical findings.</p>