Investigators for the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial describe quality control procedures for the digital rectal examination, ovarian palpation examination, transvaginal ultrasound, chest X-ray, and flexible sigmoidoscopy. These cancer screening tests are subjective and difficult to standardize. PLCO quality control procedures aim to measure and, where possible, reduce variation, across examiner and screening center, with respect to cancer screening test performance. Initial protocols stressed examiner qualifications, experience, and training; equipment specifications; examination procedures; and definitions for positive tests. The PLCO quality assurance subcommittee developed a final quality assurance plan, which included central approval and registration of PLCO examiners, direct observation of screening test performance during periodic site visits by the National Cancer Institute and coordinating center auditors, periodic analysis of screening test data, and procedures for independently duplicating or reviewing selected examinations. For each modality, the periodic data analyses examine the test-positive and the test-inadequate proportions and aim to identify divergent centers or examiners. Procedures for duplicating examinations specify feasible sample sizes for precise estimates of agreement between examiners, at each center, for each screening test modality, and over a 1-year period. These quality control procedures will help characterize the consistency and reliability of the PLCO cancer screening tests.