Abstract This is a review of several new approaches developed at or adopted by the Cooperative Prostate Cancer Tissue Resource (CPCTR) to resolve issues involved in tissue microarray (TMA) construction and use. CPCTR developed the first needle biopsy TMA, allowing researchers to obtain 200 or more consecutive cancer sections from a single biopsy core. Using radio- graphs of original paraffin blocks to measure tissue thickness we developed a method to produce TMAs with a larger number of usable sections. The modular approach to plan TMA construction is also a novel concept wherein TMAs of different types, such as tumor grade TMAs, metastasis TMA and hormone refractory tumors TMA can be combined to form an ensemble of TMAs with expanded research utility, such as support for tumor progression studies. We also implemented an open access TMA Data Exchange Specification that allows TMA data to be organized in a self-describing XML document annotated with well-defined common data elements. It ensures inter-laboratory reproduc- ibility because it offers information describing the preparation of TMA blocks and slides. There are many important aspects that may be missed by both beginners and experienced investigators in areas of TMA experi- mental design, human subjects protection, population sample size, selection of tumor areas to sample, strate- gies for saving tissues, choice of antibodies for immu- nohistochemistry, and TMA data management. Keywords Tissue microarrays Æ Experimental design Æ Immunohistochemistry Æ Prostate cancer Introduction Tissue Microarray (TMA) is a type of tissue assay that allows the researcher to simultaneously visualize and study tissues from several, even hundreds of patients. In this era of genomics and proteomics, TMAs have a dis- tinct usefulness and interest. This review article details the procedural considerations of planning and building a TMA for both novice and seasoned researchers. While our experience in design and data is focused on prostate cancer tissues as part of the Cooperative Prostate Can- cer Tissue Resource (CPCTR), these techniques are A. Kajdacsy-Balla (&) Æ J. M. Geynisman Æ V. Macias Æ S. Setty Æ N. M. Nanaji Department of Pathology, University of Illinois Chicago, 1818 W. Polk St, Chicago, IL 60607-7053, USA e-mail: aballa@uic.edu J. J. Berman Æ K. Dobbin National Cancer Institute, Bethesda, MD, USA J. Melamed Æ X. Kong Department of Pathology, New York University School of Medicine, New York, NY 20892-2590, USA M. Bosland Departments of Environmental Medicine and Urology, New York University School of Medicine, New York, NY 10016, USA J. Orenstein Æ J. Bayerl Department of Pathology, George Washington University, Washington, DC 20052, USA M. J. Becich Æ R. Dhir Department of Pathology, University of Pittsburgh Medical School, Pittsburgh, PA 15260, USA M. W. Datta Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA J Mol Hist DOI 10.1007/s10735-006-9054-5 123 ORIGINAL PAPER Practical aspects of planning, building, and interpreting tissue microarrays: The Cooperative Prostate Cancer Tissue Resource experience A. Kajdacsy-Balla Æ J. M. Geynisman Æ V. Macias Æ S. Setty Æ N. M. Nanaji Æ J. J. Berman Æ K. Dobbin Æ J. Melamed Æ X. Kong Æ M. Bosland Æ J. Orenstein Æ J. Bayerl Æ M. J. Becich Æ R. Dhir Æ M. W. Datta Æ The Cooperative Prostate Cancer Tissue Resource Received: 6 January 2006 / Accepted: 23 August 2006 Ó Springer Science+Business Media B.V. 2007