Radioimmunotherapy (RIT) with a commercially available brand of yttrium-90 (90Y)-ibritumomab-tiuxetan at the prescribed activity of 14.8 MBq/kg (0.4 mCi/kg) represents a complementary approach in the treatment of resistant/refractory B-cell non-Hodgkin's lymphoma. A trial based on higher activities is ongoing in our institute. In this paper, we report atypical pharmacokinetics and liver uptake in 2 patients. Before RIT, all patients underwent dosimetry with 111In-ibritumomab-tiuxetan. Imaging data were analyzed to obtain predicted absorbed doses to nontarget organs. Therapy was administered only if a 20-Gy-limit dose to normal organs (except red marrow) was guaranteed. Both patients we describe showed abnormal liver uptake, increasing for 6 days post injection. In patient 1, there was atypical biodistribution in whole-blood images at 16 hours, with a prevalent high liver uptake (45% at 20 hours). Injected activity (IA%) was above 40% at 26 hours in the liver and lower than 60% in the total body. In patient 2, early images showed regular biodistribution. Subsequent images showed progressive increase of liver uptake (above 25% of percent injected activity at 25 hours). Liver-absorbed doses of 51 and 53 Gy, respectively, would have resulted with the administration of the prescribed 56 MBq/kg. Following these dosimetric results, both patients did not receive the planned therapy. These findings support the recommendation to include dosimetry in high-dose RIT. © 2009 Copyright 2009, Mary Ann Liebert, Inc.