Increasingly, targeted therapies are being developed to treat malignancies. To define targets, determine mechanisms of response and resistance, and develop biomarkers for the successful investigation of novel therapeutics, high-quality tumor biospecimens are critical. We have developed standard operating procedures (SOPs) to acquire and process serial blood and tumor biopsies from patients with diffuse large B-cell lymphoma enrolled in multicenter clinical trials. These SOPs allow for collection and processing of materials suitable for multiple downstream applications, including immunohistochemistry, cDNA microarrays, exome sequencing, and metabolomics. By standardizing these methods, we control preanalytic variables that ensure high reproducibility of results and facilitate the integration of datasets from such trials. This will facilitate translational research, better treatment selection, and more rapid and efficient development of new drugs. See all the articles in this CEBP Focus section, "Biomarkers, Biospecimens, and New Technologies in Molecular Epidemiology."