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A 10-year-old spayed mixed breed dog presented with severe neurological signs. Computed tomography revealed a cranial mediastinal mass, osteolysis of the right second rib and second thoracic vertebra, tracheobronchial and mesenteric lymph node enlargement, pneumonia and pleural effusion. Magnetic resonance imaging detected lesions in the white matter of the right frontal lobe and left cerebral hemisphere with contrast-enhanced T1-weighted images showing demarcated enhancement. On cut section, the surface of the right cerebral frontal lobe and left cerebral hemisphere corticomedullary junctions were indistinct and the white matter was discoloured. Microscopically, multicentric granulomatous inflammation was seen in the brain, cranial mediastinal mass, masses on the right second rib, tracheobronchial and mesenteric lymph nodes, heart, kidneys, lungs and oesophagus. Necrosis and hyaline fungal structures were frequently observed in the centre of the granulomas. These fungi had septae, Y-shaped branching and were 2–3 μm in width. Sequence analysis of DNA from formalin-fixed paraffin-embedded samples identified the fungi as Schizophyllum commune. Based on these findings, this case was diagnosed as disseminated S. commune infection. This is the first report of granulomatous encephalitis caused by S. commune in a dog. [ABSTRACT FROM AUTHOR]