Lymphadenopathy occurs frequently in childhood caused by both reactive and neoplastic origins. Correlation of clinical findings, historical information, and patient symptoms may provide important insights into the cause of lymphadenopathy. When malignancy is suspected or if a child does not respond to antibiotic therapy, nodal biopsy or cytological examination may be undertaken to establish a diagnosis. Proper handling of pathologic materials will enhance the pathologist's ability to make an accurate diagnosis and may allow for important ancillary testing to be performed.