Soft tissue tumors are certainly not the most common specimen to come across the microscope of the practicing general surgical pathologist. However, all of us, at some point, have encountered these lesions, which can be exceedingly difficult even to the most experienced practitioners. It has been our experience that a relatively high percentage of soft tissue lesions encountered in clinical practice require ancillary diagnostic techniques, either to confirm a suspected diagnosis or to help narrow down a broad list of differential diagnostic considerations. The current issue of Pathology Case Reviews focuses on the utility of these ancillary techniques in the evaluation of soft tissue tumors. To some degree, some aspects of these discussions are aimed at providing a better understanding of the pathogenesis of soft tissue sarcomas. However, to a much larger degree, these articles are focused on the use of ancillary techniques for diagnosis, prognosis, and guiding appropriate therapy. Dr Antonio Llombart Bosch, a world-renowned expert in soft tissue tumors with years of experience with immunohistochemistry, has provided a unique perspective on some of the more useful immunohistochemical markers in the evaluation of these tumors. By necessity, this review is meant to be broad in scope, because there are innumerable markers that are potentially available to the practicing pathologist in the evaluation of this wide array of neoplasms. However, Dr Llombart Bosch and his colleague, Dr Samuel Navarro Fos, have condensed this enormous amount of information into a concise review summarizing the most important markers, using a pattern-oriented approach. Although not used nearly as commonly as immunohistochemistry, electron microscopy still plays a definite role in the evaluation of soft tissue tumors. One of the world's renowned experts in this field, Dr Brian Eyden, and his colleague, Dr Saumitra Banerjee, have provided a summary of the capabilities and limitations of ultrastructural analysis of these tumors. Given his vast experience, Dr Eyden is also able to provide a historical perspective on the use of electron microscopy in diagnostic pathology in general and in soft tissue tumors in particular. His thoughtful commentary and reasonable approach certainly help to clarify the potential role of this ancillary technique. Dr Louis Guillou discusses the role of molecular biology in the prognosis and therapy for soft-tissue tumors. The amount of data published in the last several years on this topic has been vast and is coming at an extremely rapid pace. Dr Guillou's thoughtful synthesis of this new information provides the reader with a broad understanding of the emergence of molecular pathology in the areas of prognosis and therapeutics. In the future, pathologists will undoubtedly play a greater role in providing prognostic information to the treating clinician based upon the molecular analysis of tumors. Moreover, as therapies become tailored to genetic alterations found in a given patient's tumor, pathologists will also have to continue to develop an understanding of the pathogenetic molecular alterations so frequently present in soft tissue sarcomas. One of the more cutting-edge contributions to this edition of Pathology Case Reviews is provided by Dr Torsten Nielsen and Dr Cheng-Han Lee, experts in the field of array analysis of soft-tissue sarcomas. Although this review stretches beyond diagnostic pathology, the information provided by Drs Nielsen and Lee will undoubtedly continue to shape the daily practice of the surgical pathologist in the next 5–10 years. Drs Jones, Ferguson, Wunder, and Kandel, all from the Mount Sinai Hospital at the University of Toronto, have provided a superb and concise review of testing for translocations in soft tissue sarcomas using molecular diagnostic techniques. They use a case-based approach that highlights how molecular diagnostic testing was used to solve diagnostically challenging cases. In addition, they provide a thorough and up-to-date review of this topic by condensing the rapidly emerging literature. Finally, Dr Ilan Weinreb, also from the University of Toronto, provides a fascinating description of an adamantinoma-like Ewing sarcoma which, simply stated, could not have been definitively diagnosed without the appropriate use of ancillary molecular genetic techniques, including polymerase chain reaction and fluorescence in situ hybridization. We are extremely enthusiastic about this edition of Pathology Case Reviews and hope readers will find these topics not only exciting and timely but practical in their daily surgical pathology sign out.Figure