Rationale and Objectives: To estimate and statistically compare the bias and variance of radiologists measuring the size of spherical and complex synthetic nodules. Materials and Methods: This study did not require the institutional review board approval. Six radiologists estimated the size of 10synthetic nodules embedded within an anthropomorphic thorax phantom from computed tomography scans at 0.8- and 5-mm slice thicknesses. The readers measured the nodule size using unidimensional (1D) longest in-slice dimension, bidimensional (2D) area fromlongest in-slice and longest perpendicular dimension, and three-dimensional (3D) semiautomated volume. Intercomparisons of bias (difference between average and true size) and variance among methods were performed after converting the 2D and 3D estimates to a compatible 1D scale. Results: The relative biases of radiologists with the 3D tool were -1.8%, -0.4%, -0.7%, -0.4%, and -1.6% for 10-mm spherical, 20-mm spherical, 20-mm elliptical, 10-mm lobulated, and 10-mm spiculated nodules compared to 1.4%, -0.1%, -26.5%, -7.8%, and -39.8% for 1D. The three-dimensional measurements were significantly less biased than 1D for elliptical, lobulated, and spiculated nodules. The relative standard deviations for 3D were 7.5%, 3.9%, 3.6%, 9.7%, and 8.3% compared to 5.7%, 2.6%, 20.3%, 5.3%, and 16.4% for 1D. Unidimensional sizing was significantly less variable than 3D for the lobulated nodule and significantly more variable for the ellipsoid and spiculated nodules. Three-dimensional bias and variability were smaller for thin 0.8-mm slice data compared to thick 5.0-mm data. Conclusions: The study shows that radiologist-controlled 3D volumetric lesion sizing can not only achieve smaller bias but also achieve similar or smaller variability compared to 1D sizing, especially for complex lesion shapes. © 2014.