Abstract: Methods, processing systems, and computer-readable mediums for automated designing of patient-specific cranial implants may include extracting pixel data from a DICOM file; generating a virtual skull model based on the pixel data; identifying a mid-sagittal plane of the virtual skull model; identifying a surgical hole in the virtual skull model; mirroring a reference side of the virtual skull model onto a surgical hole side of the virtual skull model; subtracting the surgical hole side from the mirrored reference side to generate a virtual cranial implant; and generating a virtual two-part mold based on the virtual cranial implant. A physical two-part mold can be 3D printed based on the virtual two-part mold, and a physical cranial implant can be constructed using the physical two-part mold.