Background: Assessment of tumor size changes is crucial in clinical trials and patient care. We compared imatinib-induced volume changes of liver metastases (LM) from gastro-intestinal stromal tumors (GIST) to RECIST and Choi criteria and their association with overall survival (OS). Methods: LM from 84 GIST patients (training and validation set) were evaluated using manual and semi-automated Computed Tomography measurements at baseline, after 3, 6 and 12 months of imatinib. The ability of uni-dimensional (1D) and three-dimensional (3D) measurements to detect size changes (increase/decrease) >= 20% was evaluated. Volumetric response cut-offs were derived from minimally relevant changes (+20/230%) by RECIST, considering lesions as spherical or ellipsoidal. Results: 3D measurements detected size changes >= 20% more frequently than 1D at every time-point (P <= 0.008). 3D and Choi criteria registered more responses than RECIST at 3 and 6 months for 3D-spheres (P <= 0.03) and at all time-points for 3D-ellipsoids and Choi criteria (P<0.001). Progressive disease by 3D criteria seems to better correlate to OS at late time-points than other criteria. Conclusion: Volume criteria (especially ellipsoids) classify a higher number of patients as imatinib-responders than RECIST. Volume discriminates size changes better than diameter in GIST and constitutes a feasible and robust method to evaluate response and predict patient benefit.