This article describes the clinical, pathological, and immunohistochemical findings associated with Cryptococcus neoformans var. grubii in a 4-year-old female Boxer dog from Uberlândia, Minas Gerais, Southeastern Brazil. Clinically, there was a swelling at the right metatarsal region and the hock joint with enlargement of regional lymph nodes. Radiographical evaluation revealed lysis of the tarsal bone; cytology demonstrated cryptococcal intralesional organisms at the swollen joint. Despite empirical antifungals therapeutic, the animal developed neurological cryptococcosis and died spontaneously. Significant pathological alterations included arthritis, lymphadenitis, and encephalitic cryptococcomas associated with numerous intralesional narrow-necked budding encapsulated yeasts. Immunohistochemistry utilising monoclonal antibodies that label C. neoformans sp. complex capsule, characterised the yeasts as C. neoformans var. grubii. Collectively, the pathological and immunohistochemical findings of this dog indicate that the intralesional organisms observed within the articular surface of the hock joint, lymph nodes, and the brain were C. neoformans var. grubii, confirming the participation of this fungal pathogen in the development of cryptococcal arthritis. In this case, the most likely pathogenesis was percutaneous inoculation with resultant abscess-like lesion, which resulted in the draining sinus, swelling of the right hind limb with progression to the articular disease. Thereafter, the fungal pathogen probably compromised the adjacent lymph nodes with subsequent haematogenous distribution to the brain, terminating with cryptococcal arthritis, lymphadenitis, and encephalitis.