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Background Primary care physicians (PCPs) play a key role in performing and referring patients for cancer screening. Understanding barriers to test use is critical to developing strategies that promote adherence to clinical guidelines, but current literature does not distinguish the extent to which barriers may be similar or unique across screening modalities. Purpose To describe PCPs' self-reported perceptions of barriers to screening for breast and colorectal cancer (CRC) and compare the top three barriers associated with these screening modalities. Methods Cross-sectional data analyzed in 2011 from a nationally representative survey of 2478 PCPs in the U.S. in 2006–2007. Results PCPs reported greater barriers for CRC screening than for mammography. Lack of patient follow-through to complete recommended screening and the inability to pay for tests were the main barriers perceived by PCPs for both types of screening. Another major barrier cited was that patients do not perceive CRC as a threat. This was a lesser concern for the well-diffused message about the need for mammography. Conclusions This is the first national study to provide a comparison of physician-perceived barriers to breast and CRC screening. Study results suggest that efforts to improve use of cancer screening, and CRC screening in particular, will require interventions at physician, practice, and health-system levels.