In today's clinical practice, the size of lymph nodes is assessed by measuring the long and the short axis in the axial plane. This study compares this approach with three-dimensional (3D) assessment. For a representative set of 49 lymph nodes, the axes in the axial plane have been measured and a 3D model has been created manually. Based on the 3D model, the real axial long and short axis as well as the three 3D axes and the volume have been computed and compared to the measured axial axes. The inter-observer variability is around 10% for all measured lengths and almost 16% for the computed volume. The average relative error of the measured long (short) axial axis is 9.73% (24.57%) to the computed axial axis and 25.05% (19.97%) to the computed 3D axis, respectively. The product of the axial long axis and the square of the axial short axis provides best correlation to the volume. This study confirms Response Evaluation Criteria In Solid Tumours 1.1 that measuring the short axis is more robust than measuring the long axis because of less impact of the node's spatial orientation. Nonetheless it is shown that considering both axes is a better prognostic factor for the volume than measuring the short axis only. Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.