Background: Peripheral lymphadenopathy affects most children at least once in a lifetime and represents a major reason for concern for children and their caregivers, although the malignancy is an uncommon cause of lymphadenopathy in this age group. Viral infections such as infectious mononucleosis is a common cause of bilateral cervical lymphadenitis or generalized lymphadenopathy in older children. Pyogenic bacteria and granulomatous diseases usually cause unilateral lymph node enlargement. We aimed to identify the most common causes of peripheral lymphadenopathy in hospitalized children and to determine the clinical, laboratory and ultrasound characteristics that enable easy and accurate etiological diagnosis.Methods: We performed a cross-sectional study including 139 children who were hospitalized because of peripheral lymphadenopathy and in whom the etiological diagnosis could be ascertained. Blood tests, including serology for Epstein-Barr virus and Bartonella hensleae were performed in all children, and ultrasound of lymph nodes was performed in 113 (81.3%) of them. Incision with the detection of bacteria, aspiration biopsy or extirpation of lymph nodes were performed when clinically indicated. The Mann-Whiney U test or chi-squared test and a (multinomial) regression analysis was performed to compare epidemiological, clinical, laboratory and ultrasound characteristics of patients with three most common etiologies.Results: Lymphadenopathy was generalized in 9 (6.5%) patients. 114 (82.0%), 6 (4.6%), 6 (4.6%) and 4 (3.1%) patients presented with localized lymphadenopathy in the cervical, axillary, supraclavicular and inguinofemoral areas, respectively. Malignant etiology was established in only 3 (2.2%) patients. Bacterial lymphadenitis, infectious mononucleosis (IM) and cat scratch disease (CSD) was diagnosed in 66 (47.5%), 31 (22.3%) and 29 (20.9%) patients, respectively. Bacterial lymphadenitis was significantly associated with neutrophilia (p<0.01) and increased C-reactive protein levels (p<0.01). IM was associated with pharyngitis (p<0.01), leukocytosis without neutrophilia (p=0.03), increased blood liver enzyme levels (p<0.01) and lactate dehydrogenase levels (p<0.01). CSD was associated with recent contact with a cat (p<0.01), absence of a fever (p<0.01) and normal white blood cell count (p<0.01).Conclusions: Thorough history and clinical examination in combination with a few basic laboratory tests enable fast and accurate differentiation between the most common etiologies of lymphadenopathy in children to avoid unnecessary procedures and hospitalizations.