Guam disease (ALS—parkinsonism—dementia complex) is a rare endemic condition of progressive generalized degeneration of CNS neurons. Despite the apparent association of the disease with the Pacific region, sporadic cases of Guam disease have been described in other countries of the world, where the term “ALS with frontotemporal dementia” is used to refer to it. The authors cite their own clinical case of the disease, as well as discuss aspects of the clinical presentation, etiology, pathogenesis, diagnosis, and differential diagnosis of similar conditions.