Abstract: Several recent efforts in the radiation biology community worldwide have amassed records and archival tissues from animals exposed to different radionuclides and external beam irradiation. In most cases, these samples come from lifelong studies on large animal populations conducted in national laboratories and equivalent institutions throughout Europe, North America, and Japan. While many of these tissues were used for histopathological analyses, much more information may still be obtained from these samples. A new technique suitable for imaging of these tissues is x-ray fluorescence microscopy (XFM). Following development of third generation synchrotrons, XFM has emerged as an ideal technique for the study of metal content, speciation, and localization in cells, tissues, and organs. Here the authors review some of the recent XFM literature pertinent to tissue sample studies and present examples of XFM data obtained from tissue sections of beagle dog samples, which show that the quality of archival tissues allows XFM investigation.