Cryptococcosis is a worldwide-distributed fungal disease affecting humans and animals and is considered the most common systemic mycosis in cats. Classically, the clinical presentation of cryptococcal infection in cats consists of solitary or multiple nodules located on the planum nasale or the bridge of the nose. Bone involvement as cryptococcal osteomyelitis is a rare clinical entity of cryptococcosis. Herein, this case report describes a domestic shorthair cat with osteomyelitis of the mandibular bone resulting from Cryptococcus spp. infection. During the physical examination, a subcutaneous mass measuring approximately 6 cm in diameter was identified at the mandibular region. Cytological evaluation revealed numerous encapsulated yeasts resembling Cryptococcus spp. Histopathological examination revealed multifocal to coalescent subcutaneous granulomatous inflammation with a large number of spherical yeasts surrounded by a clear capsule. These yeasts were positive for periodic acid-Schiff (PAS) staining. The cat was successfully treated with a combination of itraconazole therapy and surgical management. To the author's knowledge, this is the first clinical report of oral cryptococcal osteomyelitis in a cat.