In children with localized adenopathy that persists past to weeks, ill-appearing children, and children with generalized lymphadenopathy, further evaluation should be performed, guided by the differential diagnosis that was formed based on history and physical examination Any suspicion of malignancy warrants assessment with CBC with differential and peripheral blood smear examination, as well as chest radiograph to assess for mediastinal adenopathy In addition, lactate dehydrogenase and uric acid may be elevated, indicating tissue damage and rapid cell turnover Inflammatory markers, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are nonspecific, but may be elevated in children with systemic inflammatory diseases and can be helpful in monitoring response to treatment In children with nonspecific infectious symptoms, viral serologies (EBV, CMV, HIV) may be informative As indicated by history and examination, serology for B henselae, or tuberculin skin testing or serum testing for M tuberculosis may be performed Various imaging modalities may aid in the diagnosis of lymphadenopathy, including ultrasound (US), CT, and MRI The type of diagnostic radiology necessary to evaluate lymphadenopathy depends on the location and chronicity of the lymph node(s) In efforts to limit radiation to doses as low as reasonably achievable (ALARA principle), US has proven to be a very effective, noninvasive, inexpensive, highly available, and nonradiating type of imaging to evaluate lymphadenopathy in children US can distinguish between simple node enlargement and a suppurative lesion with higher sensitivity than CT Color Doppler imaging can demonstrate increased blood flow to inflamed lymph nodes as well as a hypoechoic (dark) center in a suppurative node Characteristics of the grouping of the lymph nodes can also aid the radiologist in narrowing the patient’s differential diagnosis It is important to note that children age >1 year with neck swelling ≤3 days are at low risk of having US findings that require surgical drainage CT may be preferred in the evaluation of lymphadenopathy when greater anatomic detail is desired, as in a preoperative radiologic evaluation or in the evaluation of deep cervical space neck infections Contrast-enhanced CT is more sensitive than US for the diagnosis of an abscess but lacks specificity due to the similar radiologic appearance of frank pus and phlegmonous changes MRI may provide these fine details without ionizing radiation, but the cost of imaging and need for sedation make CT a more preferable and easily accessible modality when accessed from the emergency department Finally, in the course of evaluation of lymphadenopathy, the decision to perform a biopsy on an enlarged node remains a clinical one In general, early node biopsy should be considered in children who are ill with systemic symptoms, persistent fever, or weight loss Deep inferior cervical or supraclavicular adenopathy, with or without an abnormal chest film, is pursued aggressively with biopsy, given the concern for malignancy, in particular lymphoma Beyond this, in the face of an otherwise negative diagnostic workup, serial measurement over a period of weeks showing progressive or rapid enlargement of the affected node raises suspicion for malignant disease and biopsy should be strongly considered Biopsy should also be considered if an enlarged node fails to regress in size after approximately weeks of observation