Different error detection methods yield different error proportions and have variable benefits for surgical pathology divisions with limited resources. We performed a nonconcurrent cohort study at a large institution that practices subspecialty surgical pathology sign-out to compare the effectiveness and usefulness of error detection using a targeted 5% random review process and a focused review process. Pathologists reviewed 7,444 cases using a targeted 5% random review process and 380 cases using a focused review process. The numbers of errors detected by the targeted 5% random and focused review processes were 195 (2.6% of reviewed cases) and 50 (13.2%), respectively (P < .001). The numbers of major errors for the targeted 5% random and focused review processes was 27 (0.36%) and 12 (3.2%), respectively (P < .001). Focused review detects a higher proportion of errors and may be more effectively used for design of error reduction initiatives.