The diagnosis of bone tumors is challenging and depends on optimal processing of specimens as well as integration of radiographic and clinical information. The correct diagnosis will often require ancillary techniques such as immunohistochemistry, flow cytometry and molecular or cytogenetic analysis. From a pathologist's standpoint, optimal processing of specimens is paramount and often requires some foreknowledge of anticipated diagnosis in order to triage a specimen properly. The type of specimen, small vs. large, will often dictate the type of information that should be reported by the pathologist. Small specimens, including core biopsies and small incisional biopsies, are often obtained for primary diagnosis and as such, require a different approach to management. In addition to assuring the adequacy of the specimen for diagnosis, the pathologist will often need to triage these materials for appropriate ancillary studies. Large specimens, including amputations and large resections, pose a different set of technical problems for handling and processing. In this setting, information such as grading, staging, and marginal status become more crucial and the subsequent processing of the specimen should be handled in a very standardized manner to facilitate optimal pathologic reporting. This chapter offers a concise but detailed review for handling both types of bone tumor specimens. © 2014 Springer Science+Business Media New York.