Diagnostic errors in surgical pathology can affect patient care, particularly in cancer diagnoses, where misdiagnosis can lead to the inappropriate initiation of chemotherapy. These high stakes have led many institutions to routinely require outside case review prior to treatment. This study at Mayo Clinic examined more than 71,000 pathology cases. Major diagnostic disagreements were found 0.6% of the time, and the changed diagnosis affected both treatment and prognosis more than 90% of the time. Despite the low prevalence of revised diagnoses, the gravity of these cases underscores the value of outside pathology case review. An AHRQ WebM&M commentary highlights a diagnostic pathology error that nearly led to the incorrect initiation of chemotherapy.