This study examined empirical evidence for clinical utility of the Wechsler Intelligence Scale for Children, fourth edition (WISC-IV) cancellation subtest by comparing data from 597 clinical and 597 matched control children. The results of dependent t and sequential logistic regression analyses demonstrated that (a) children with intellectual disabilities, motor impairments, head injuries, Autistic/Aszperger’s disorder, ADHD and learning disabilities, and mathematics disorder showed significant deficits on the cancellation subtest; (b) children with intellectual disabilities and Asperger’s disorder benefited when stimuli were randomly aligned, but children with ADHD benefited from structured conditions; (c) beyond the full-scaled IQ (FSIQ) and General Ability Index (GAI)–Cognitive Proficiency Index (CPI) discrepancy scores, the cancellation subtest added unique diagnostic power to identify children with reading disorders, mild intellectual disabilities, closed head injuries, and motor impairments. These results suggest the utility of the cancellation subtest in clinical assessment.