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To differentiate reactive from malignant lymphadenopathy by using color Doppler ultrasonographic (US) findings of intranodal blood vessels.Color Doppler US was performed in 117 lymph nodes in 100 consecutive patients before performance of surgical biopsy (47 nodes), neck dissection (62 nodes), or high-speed core biopsy (eight nodes). The presence of malignant changes in intranodal angioarchitecture (focal perfusion defects, aberrant course of central vessels, displacement of intranodal vessels, subcapsular vessels) was evaluated in each node. Inter- and intraobserver variability were evaluated.Histopathologic examination demonstrated 48 reactive lymph nodes (longest diameter +/- standard deviation, 13.5 mm +/- 6.0), 56 nodal metastases (longest diameter, 19.2 mm +/- 8.8), 12 malignant lymphomas (longest diameter, 23.2 mm +/- 10.5), and one node infiltrated by Langerhans cell histiocytosis. At color Doppler US, 103 (88%) nodes were classified correctly, with a specificity of 77% and a sensitivity of 96%. Reproducibility was 90%-96% (kappa = 0.79-0.91, P.001).Color Doppler US is a reliable and reproducible method for help in the differentiation between reactive and malignant alterations of superficial lymph nodes by using findings of intranodal angioarchitecture.