The goal of this Funding Opportunity Announcement (FOA), is to solicit applications from independent, multi-disciplinary teams to undertake a comprehensive molecular and cellular characterization of tumor tissue, cell, and microenvironment components to distinguish screen-detected early lesions from interval and symptom-detected cancers.Individual research teams will pursue one or more aspects of molecular and cellular analysis of one or more of the specified tumor sites (breast, prostate, lung, melanoma, and pancreas).Use of enabling approaches and technologies will be encouraged to determine both the cellular and molecular phenotypes of early lesions, to assess the degree to which the behavior of these lesions is predictable or stochastic, and to allow better predictions of the fate of early lesions.To achieve the goal of a comprehensive characterization of screen-detected lesions, each research team should include cancer researchers and clinicians with multi-disciplinary expertise.The individual research teams funded through this FOA are expected to participate in a collaborative Consortium.In addition to individual studies, a major collaborative effort within the Consortium will be the establishment of an annotated biospecimen repository of screen-detected lesions and interval cancers.Research teams will also be expected to share results freely within the Consortium, and develop trans-Consortium collaborative projects that make use of the combined expertise and technological capabilities present in all of the teams.During the final selection of the teams to be funded through this FOA, NCI will, if possible, attempt to ensure that most of the specified tumor sites are represented.