<p>Lymphoid malignancies are a heterogeneous group of tumors that have distinctive clinical and biological behaviors. The increasing prevalence of disease reflects both treatment advances and the fact that some of these tumors are indolent. The ability to determine treatment needs at diagnosis remains problematic for some of the tumors, such as in follicular lymphomas. Major clinical advances will likely depend on precision oncology that will enable identification of specific disease entities, prognostic determination at diagnosis, and identification of precise therapeutic targets and essential pathways. However, refinement in diagnostic evaluation is an evolving science. The ability to determine prognosis at diagnosis is variable, and for many of the lymphoid malignancies prognosis can only be made after initial treatment. Clinical trials that aim to evaluate specific features of these diseases are required in order to advance clinical practice that meaningfully addresses this important public health challenge. Herein, we describe the process and general recommendation from the National Cancer Institute (NCI) clinical trials planning meeting in November 2014 to address clinical trial design and biomarker proposals in the context of NCI-supported lymphoma clinical trials in the National Clinical Trials Network.</p>