Improving the quality of oncologic pathology diagnosis is immensely important as the overwhelming majority of the approximately 1.6 million patients who will be diagnosed with cancer in 2010 have their diagnoses established through the pathologic interpretation of a tissue sample. Millions more patients have tissue samples obtained to rule out cancer and do not have cancer. The majority of studies on the quality of oncologic pathology diagnoses have focused on patient safety and have documented a variety of causes of error that occur in the clinical and pathology laboratory testing phases of diagnostic testing. The reported frequency of a diagnostic error made by oncologic pathology depends on several factors, such as definitions and detection methods, and ranges from 1% to 15%. The large majority of diagnostic errors do not result in severe harm, although mild to moderate harm in the form of additional testing or diagnostic delays occurs in up to 50% of errors. Clinical practitioners play an essential role in error reduction through several avenues such as effective test ordering, providing accurate and pertinent clinical information, procuring high-quality specimens, providing timely follow-up on test results, effectively communicating on potentially discrepant diagnoses, and advocating second opinions on the pathology diagnosis in specific situations. CA Cancer J Clin 2010;60:139–165. © 2010 American Cancer Society, Inc.