A 5-year-old 5.5-kg castrated male Italian Greyhound was evaluated for bone pain, generalized hyperesthesia and fever. Physical and orthopedic examination revealed non-specific bone pain and hyperesthesia; radiographs were then performed. Radiological findings included smooth to irregular periosteal reaction on the caudal, lateral and medial aspect of the proximal right humeral diaphysis. Moth-eaten to permeative lysis was present on the humeral head and metaphysis with mild associated sclerosis. Because the dog’s clinical signs worsened despite instituted medical management, synovial fluid samples were obtained and submitted for cytological analysis and culture. Surgical biopsy specimens were obtained from the right proximolateral diaphysis of the right humerus. Results of histochemical analysis, cytology and culture of bony tissue and blood were negative for bacterial or fungal agents. These clinical, imaging, and histopathologic findings were compatible with Chronic Recurrent Multifocal Osteomyelitis (CRMO). To the author’s knowledge, this is the first report of chronic recurrent multifocal osteomyelitits in a dog. CRMO should be considered as a differential diagnosis in dogs with signs of bone pain with or without fever. Further investigation into therapeutic treatments and causative etiologies in veterinary patients is warranted.