A phantom (44) is used to calibrate a multi-modality imaging system (10) that includes a nuclear imaging system (12) and a CT scanner (14). The phantom (44) includes marker receiving cavities (96) positioned at fixed locations in the phantom, in which markers (46) are removably placed. The markers (46) include CT markers (90), which are imageable by the CT scanner (14), and radioisotope markers (48), which are imageable by the nuclear imaging system (12). The radioisotope markers (48) are disposed into wells (92) provided at a center of mass of each disk-like CT marker. The markers (46) have a label (94) identifying its isotope. The phantom (44), rigidly affixed to a couch (32), is imaged by the nuclear imaging system (12) and by the CT scanner (14). A transformation processor (72) calculates a transformation which brings centroids of the CT markers (90) in a CT image and the radioisotope markers (48) in a nuclear image into alignment.