A case of central nervous system protothecosis in a dog is reported. A three-year-old male Maremma sheepdog was referred with a two month history of diarrhoea associated with progressive tetraparesis, depression and right circling. Stupor, severe proprioceptive deficits, bilateral decreased thoracic limb flexor reflexes and bilateral deficit of the menace reaction were detected on neurological examination and a multi-focal neurological localisation was suspected. Histopathological evaluation revealed multi-focal granulomatous foci in the thalamus, hippocampus and caudal brainstem containing numerous oval-rounded organisms with a thick, periodic acid-Schiff-positive and Gomori’s methenamine silver-positive cell wall, a basophilic cytoplasm and one nucleus. Scattered sporangia containing two to four endospores were also observed. Morphological features were consistent with Prototheca species. Ultrastructurally, numerous degenerated algae were present within macrophages mainly lacking nuclei and cytoplasmic organelles. Generally, protothecosis in dogs is characterised by systemic signs because of a multi-organ involvement, and haemorrhagic colitis or ophthalmologic signs are the most frequent presenting signs. However, protothecosis should be added, also in Europe, to the list of the differential diagnoses in adult dogs with a multi-focal neurological localisation even in absence of other clinical signs.