Chronic recurrent multifocal osteomyelitis (CRMO) or also called chronic non-bacterial osteomyelitis (CNO) is the most common autoinflammatory bone disease. It is characterized by the presence of symptomatic and non-symptomatic bone lesions, mono or multifocal. The main sites involved are the metaphyses of the long bones, the bones of the pelvis, the vertebrae, the clavicle, the mandible. Local symptoms include pain, swelling, and warmth in the absence or presence of fever. The inflammatory process can involve the skin (palmoplantar pustulosis or acne) and the intestine. Diagnosis is complex and uses imaging techniques (X-ray, total-body MRI, scintigraphy) as well as common laboratory tests aimed at identifying an inflammatory state. In doubtful cases, especially in the monofocal forms, it is mandatory to perform a biopsy examination to rule out malignancy. The differential diagnosis includes neoplastic diseases, chronic infections, metabolic diseases, traumatic outcomes. Treatment is not standardized and involves the use of non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, sulfasalazine, methotrexate, TNF inhibitors and bisphosphonates based on the experience of the individual centers. We report the experience of our Center (Operative Unit of Pediatrics S. Anna Hospital in Ferrara) with the description of 3 clinical cases, diagnosed from 2016 to 2018, treated with bisphosphonates with good clinical response and remission in two of them, while one patient had an adverse reaction to pamidronate and was subsequently successfully treated with methotrexate.