Hypertrophic osteopathy (HO) is a diffuse periosteal reactivity of long bones and of poor prognosis as most cases died after short time or euthanized at the time of diagnosis. Early diagnosis is greatly important. Therefore, the present study aimed to investigate the clinical and different imaging features of HO in 12 dogs and hematological and biochemical changes. Twenty-two dogs were included in this study; 10 apparently healthy dogs were used as controls, and 12 dogs were diagnosed with HO. Diagnosis of HO-affected cases was based on a range of clinical, laboratory, and histopathological examinations as well as different imaging techniques. Two forms of HO were diagnosed: pulmonary (n=5) and extrapulmonary (n=7) HO. In pulmonary HO, pneumonia was recorded in five dogs. However, in extrapulmonary HO, mammary gland tumors and skin tumors were recorded in five and two dogs, respectively. Symmetrical non-edematous soft tissue swelling at the lower parts of the limbs with intensive bone proliferation and periosteal reactivity in the tubular long bones was observed. Anemia and leukocytosis, mainly lymphocytosis (50%) or neutrophilia (45%), and elevated serum globulin, alkaline phosphatase, and C-reactive protein levels were the significant associated laboratory findings. The use of different diagnostic techniques was greatly important in the diagnosis of HO in dogs and provided information on the prognosis of such cases.