Prior to the 90Y-ibritumomab tiuxetan (Y2B8) therapy, imaging is performed to verify the expected biodistribution of 111In-ibritumomab tiuxetan (In2B8). In order to determine the indication of radioimmunotherapy with Y2B8, the interpretation criteria for altered biodistribution of In2B8 was established. A phase II study of Y2B8 in patients with relapsed or refractory indolent B-cell lymphoma was performed in nine institutions in Japan. After the completion of the rituximab infusion at 250 mg/m2, 130 MBq of In2B8 was administered intravenously over 10 minutes. Gamma-camera imaging was performed at 2-24 hrs, 48-72 hrs, and 90-144 hrs. Images were interpreted by two investigators including a nuclear physician at the individual institution according to the protocol defined criteria to determine the indication of the radioimmunotherapy. Forty-seven cases were enrolled in the study, and 45 cases underwent In2B8 scintigraphy. After the completion of the study, central assessment of the scintigram was performed by three nuclear physicians according to both the criteria of the phase II study and the latest version of the package insert of Zevalin in the United States of America. Two cases were judged as altered biodistribution based on both criteria. They demonstrated diffusely increased bone marrow uptake. The protocol defined criteria revealed additional two cases with altered biodistribution. They showed increased splenic uptake with facilitated blood clearance without increase in the bone marrow uptake. They received Y2B8 and no increment in the adverse event was noted as compared with cases with expected biodistribution. Then this type of biodistribution was not considered altered biodistribution. Increased focal bone marrow uptake was noted in other two cases. They were also considered within the limit of expected biodistribution. The present study recommends the following criteria for altered biodistribution of In2B8. 1) Diffusely increased bone marrow uptake simulating the super scan on bone scintigraphy, 2) Prominent uptake in all of the liver, spleen, and bone marrow, 3) Uptake in the lung, kidney, and intestine without lymphoma higher than the liver.