Systems and methods are provided for automatic 3D segmentation of abnormal anatomical structures such as colonic polyps, aneurisms or lung nodules, etc., in 3D medical imaging applications. For example, systems and methods for 3D lesion segmentation implement a centroid-based coordinate transformation (e.g., spherical transformation, ellipsoidal transformation, etc.) to transform a 3D surface of the lesion from an original volume space into, e.g., a spherical or ellipsoidal coordinate space, followed by interpolation of the transformed lesion surface to enable accurate determination of a boundary between a lesion and surrounding normal structures.