The purpose of this study was to develop a 3D quantification technique to assess the impact of imaging system on depiction of lesion morphology. Regional Hausdorff Distance (RHD) was computed from two 3D volumes: virtual mesh models of synthetic nodules or “virtual nodules” and CT images of physical nodules or “physical nodules”. The method can be described in following steps. First, the synthetic nodule was inserted into anthropomorphic Kyoto thorax phantom and scanned in a Siemens scanner (Flash). Then, nodule was segmented from the image. Second, in order to match the orientation of the nodule, the digital models of the “virtual” and “physical” nodules were both geometrically translated to the origin. Then, the “physical” was gradually rotated at incremental 10 degrees. Third, the Hausdorff Distance was calculated from each pair of “virtual” and “physical” nodules. The minimum HD value represented the most matching pair. Finally, the 3D RHD map and the distribution of RHD were computed for the matched pair. The technique was scalarized using the FWHM of the RHD distribution. The analysis was conducted for various shapes (spherical, lobular, elliptical, and speculated) of nodules. The calculated FWHM values of RHD distribution for the 8-mm spherical, lobular, elliptical, and speculated “virtual” and “physical” nodules were 0.23, 0.42, 0.33, and 0.49, respectively.