Objective: The aim of this study was to evaluate the frequency, demographic and clinical characteristics of pediatric patients with extremely elevated erythrocyte sedimentation rate (ESR) in a reference children's hospital, and to improve clinicians' ability to use extremely elevated ESR in the differential diagnosis. Material and Methods: A retrospective cohort study was conducted to examine the clinical data of pediatric patients with extremely elevated ESR ( ≥100 mm/h). The patients were divided into 6 main groups according to their diagnosis as infectious, non-infectious inflammatory disease (NIID), malignancy, nephrologic, miscellaneus and unknown. Then, the specific sub-diagnoses of the patients were determined and evaluated. Clinical and laboratory data of the patients were recorded. Results: We analyzed the results of a total of 3166 patients with high ESR (≥20 mm/h) and 189 (5.96%) patients with extremely elevated ESR were included in the final analysis. The most common etiology of extremely elevated ESR was NIID (35.9%), followed by infections (33.3%), malignancies (19.0%) nephrologic (2.6%), miscellaneus (4.7%) and unknown (4.2%). The most common specific diagnosis was acute rheumatic fever, Kawasaki disease, lymphadenitis and leukemia. The high ESR was only negatively correlated with hemoglobin and albumin levels. Conclusion: Identifying the most common diseases that cause extreme ESR elevation in children can help clinicians in the differential diagnosis of diseases but it cannot be used as a screening tool for diseases.