BACKGROUND: The purpose of this study was to determine the accuracy of two semi-quantitative scoring systems to assess response to (131)I-metaiodobenzylguanidine (mIBG) therapy in recurrent neuroblastoma. PROCEDURES: Diagnostic mIBG scan pairs (n = 57) were collected for patients who underwent (131)I-mIBG therapy for relapsed neuroblastoma. Two scoring systems were designated: Method 1, which divided the body into nine segments to view osteomedullary lesions with an additional tenth segment to assess soft tissue involvement; and Method 2, which divided the body into seven segments without a corresponding compartment for soft tissue involvement. Four nuclear medicine physicians independently assigned extension and intensity scores utilizing both methods, and separately recorded their impression of whether the post-therapy scan had improved, not changed, or worsened. Inter- and intra-observer concordance and correlation with overall response and progression-free survival (PFS) were performed. RESULTS: Method 1 produced the highest inter-observer concordance and was used to calculate the relative extension scores (post-therapy score divided by pre-therapy score), which correlated significantly with overall response. Patients who achieved complete response (CR) or partial response (PR) (n = 21) had lower relative extension scores, compared to those without response (P < 0.001). The readers' overall impression associated highly (P < 0.001) with the relative extension scores though results were less quantitative. Concordance was higher if initial scores were >5. Relative extension score did not predict PFS. CONCLUSION: Semi-quantitative scoring of mIBG scans provides a more reliable method of assessing response in patients with relapsed neuroblastoma than qualitative impression. The reproducibility and high inter-observer concordance makes mIBG score an important component of overall response criteria in patients with recurrent neuroblastoma.