System and method for XRD-based false alarm resolution in computed tomography (“CT”) threat detection systems. Following a scan of an object with a megavoltage CT-based threat detection system, a suspicious area in the object is identified. The three dimensional position of the suspicious area is used to determine a ray path for the XRD-based threat detection system that provides minimal X-ray attenuation. The object is then positioned for XRD scanning of the suspicious area along this determined ray path. The XRD-based threat detection system is configured to detect high density metals (“HDMs) as well as shielded Special Nuclear Materials (“SNMs”) based on cubic or non-cubic diffraction profiles.