A recent advance in radiation oncology depends on a remarkable progress in external radiotherapy (RT) techniques including stereotactic irradiation (STI), three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and image-guided radiation therapy (IGRT). Precise RT planning and positioning has often been carried out with an error of ±1 mm for some patients; however, the accuracy is not enough for molecular targeting. Molecular imaging has been utilized for IGRT planning recently and is expected to develop molecular targeted radiotherapy. But, the majority of the imaging for clinical use is 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT, and it is actually difficult to delineate molecular target precisely using IGRT. Combination of external RT and molecular targeted agents appears to be reasonable compared with molecular targeted external RT. Radionuclide therapy is achieved by using radioisotopes (iodine-131, strontium-89, yttrium-90, etc.) that usually emit beta particles for selective delivery of radiation to target tumor cells or organs, but not always to molecules. Radioimmunotherapy is a type of radionuclide therapy that combines monoclonal antibody treatment and radiation therapy. An yttrium-90-labeled CD20-directed antibody (ibritumomab tiuxetan) is used for some types of B-cell non-Hodgkin lymphoma (follicular lymphoma, mantle cell lymphoma, etc.) The antibody binds to the CD20 antigen on the surface of B-cell lymphoma cells specifically and the radiation emitted from the radioactive isotope damages or kills the lymphoma cells and some nearby, and has often showed promising results for patients with relapsed or refractory lymphoma. This treatment is a typical radioimmunotherapy and sometimes classified as a molecular targeted radiotherapy. Further possibility of molecular targeted radionuclide therapy will be promising.