To compare changes in RECIST, anatomical volume, mRECIST, and volumetric diffusion-weighted Imaging parameters (3D apparent diffusion coefficient (ADC) measurements), with pathological analysis of hepatocellular carcinoma (HCC) treated by (90)Yttrium radioembolization (Y90). 21 patients were treated by Y90 as a sole treatment modality for solitary, >2 cm HCC that underwent liver transplantation. MRI at baseline, 1 and 3 months post-Y90, and tumor pathological findings on explants were reviewed in all patients. Compared to baseline (RECIST/volume: 3.6 cm/17.7 cm(3)), RECIST and volume were not modified after Y90 (1 month, p = 0.28/0.09 RECIST/tumor volume; 3 months, p = 0.28/0.54). In contrast, mRECIST (3.3-1.4 cm, p < 0.001), mean ADC (0.185-1.093 mm(2)/s × 10(-3), p = 0.04), and ADC standard deviation (STD) (0.041-0.201 mm(2)/s × 10(-3), p = 0.0496) changed as earlier as 1 month post-Y90. ADC STD % change was higher in ADC responding lesions than non-responding lesions at 1 month (p = 0.002) and 3 months (p = 0.008). All lesions exhibited necrosis on pathological analysis (11 partially viable, 10 complete pathological necrosis (CPN)) but no imaging criterion was able to predict CPN. mRECIST (±ADC) at 1 (κ ± ADC = 0.08/0.06) or 3 months (κ = -0.06/-0.06) were poor predictors of pathological response. As soon as 1 month post-treatment, mRECIST and volumetric ADC performed better than traditional size RECIST or volumetric parameters in detecting imaging response to Y90; however, CPN cannot be predicted by any criteria. Improvements in methodologies to assess response and identification of better surrogates are awaited.