Context In an era in which testing of patient tumor material for molecular and other ancillary studies is of increasing clinical importance for selection of therapy, the ability to test on small samplings becomes critical. Often, small samplings are rapidly depleted in the diagnostic workup or are insufficient for multiple ancillary testing approaches. Objective To describe technical methodologies that can be implemented to preserve and maximize tissue for molecular and other ancillary testing. Data Sources Retrospective analysis of a case cohort from the University of Colorado, description of techniques used at the University of Colorado, and published literature. Conclusions Numerous techniques can be deployed to maximize molecular and other ancillary testing, even when specimens are from small samplings. A dedicated process for molecular prioritization has a high success rate, but also increases workload, which must be factored into establishing such a process. Additionally, establishing high-fidelity communication strings is critical for success of dedicated molecular prioritization of samples. Numerous approaches can be deployed for alternative specimen types, and several technical approaches can also aid in maximizing small specimens.