Disseminated Scedosporium prolificans infection in a 1-year-old female spayed German Shepherd dog is described. Clinical signs were predominantly associated with fungal pyelonephritis and the organism was cultured from the urine. The dog was treated with itraconazole and later, terbinafine was added. Subsequent antifungal susceptibility testing of the isolate showed it to be resistant to all available antifungal drugs. The dog was euthanased because of acute abdominal haemorrhage and associated clinical deterioration. Postmortem examination revealed extensive pyogranulomas containing fungal organisms in the renal parenchyma, myocardium, bone marrow, skeletal muscle, liver, lung, spleen, multiple lymph nodes and pancreas.