A residual mediastinal mass is a common finding during and/or after treatment for bulky mediastinal lymphoma and represents a difficult diagnostic problem. For correct therapy modulation, fibrosis must be distinguished from active disease. To assess diagnostic imaging potentials in the characterization of residual masses, 41 patients with bulky mediastinal lymphoma were examined with CT, MRI and Ga67-SPET; 92 examinations were performed for each technique: 14 before treatment, 42 during and after chemotherapy, 13 after radiotherapy and 23 six months after the end of treatment. CT provides useful pieces of information on tumor size but fails to depict tissue changes: therefore, only MR and SPET results were considered and compared with clinico-biological and follow-up findings. MRI and SPET were often in agreement with each other (78/92 cases) and with clinical data (98.7%); each examination yielded only one false positive. In case of disagreement (14/92 patients), MRI yielded more false-positive findings because it failed to differentiate neoplastic tissue from treatment-related conditions, i.e., granulation tissue, inflammation, necrosis, early fibrosis. In contrast, negative MR results were more reliable, MR negative predictive value being 100%. Ga67-SPET exhibited high sensitivity (97.1%) and specificity (91.2%), with fewer false positives than MRI (5 vs. 10). In conclusion, both examinations were accurate in the characterization of residual mediastinal masses during and after therapy, but MRI had higher sensitivity and Ga67-SPET higher specificity. Therefore, the authors acknowledge the complementary role of these two techniques and the necessity of an integrated approach, i.e., combined MRI and Ga67-SPET or CT and Ga67-SPET.