Background: Chronic Recurrent Multifocal Osteomyelitis (CRMO) is a rare aseptic autoinflammatory disease with a wide and vague clinical presentation that often mimics infection, malignancy, or benign conditions, leading to a delayed diagnosis. We aimed to evaluate the clinical characteristics, differential diagnoses from evaluating pediatric orthopaedic surgeons, and compared the number of patients that could have avoided a biopsy in 80 patients with CRMO.Methods: Children diagnosed with CRMO at a single tertiary pediatric hospital in the United States between 2012 and 2022 who were evaluated by a pediatric orthopaedic surgeon were retrospectively reviewed. The differential diagnoses from the surgeons were recorded from their initial presentation. The Jansson criteria and Bristol Criteria were retrospectively applied to evaluate patients who could have been spared a biopsy.Results: 80 children (65% female) with CRMO were identified. The mean age at diagnosis was 10.28 ± 3.52 years, follow-up of 37.13 ± 27.67 months, and delay in diagnosis of 6.21 ± 9.75 months. Common presenting symptoms were antalgic gait (45%), local inflammation (30%), and fever/fatigue (26.25%). 58% presented clinically with unifocal symptoms, but 81% had multifocal disease on imaging. Radiographs were unremarkable in 35%, had periosteal reaction/sclerosis (23%), or a lytic lesion (22%). On MRI, 72% of patients had marrow edema, periosteal reaction (23%), and/or osteitis (19%). 69% of patients received a whole-body MRI, and 75% received a bone biopsy. The femur, tibia, pelvis, and spine were involved in >30% of patients. The most common initial differential diagnoses were