Background: While associations between conduct disorder (CD), oppositional defiant disorder (ODD), attention deficit hyperactivity disorder (ADHD), and interpersonal callousness (IC) symptoms and delinquency onset are well established, less is known about whether these characteristics differentiate desisting and persisting delinquency. The current study examined whether childhood and adolescent CD, ODD, ADHD, and IC symptoms uniquely distinguished boys who exhibited persisting versus desisting delinquency from adolescence into adulthood. Methods: Participants were 503 boys (57% African American) repeatedly assessed from ages 7 to 25. Associations between childhood and adolescent CD, ODD, ADHD, and IC symptoms and desisting and persisting delinquency were examined independently and after controlling for their co-occurrence and multiple covariates. Results: Conduct disorder and IC symptoms in childhood and adolescence were higher among boys whose delinquency persisted into adulthood relative to those boys whose delinquency desisted across time. After controlling for the overlap between symptoms of ADHD, ODD, CD and IC, only adolescent CD and IC symptoms emerged as unique predictors of the differentiation between persisters and desisters. Moreover, adolescent CD and IC symptoms continued to contribute unique variance even after childhood levels of these characteristics were accounted for. Conclusions: Boys with elevated levels of CD and IC symptoms in childhood and adolescence are at risk for exhibiting a pattern of delinquency that persists from adolescence into adulthood. Intervention efforts designed to prevent chronic delinquency should target youth with co-occurring CD and IC symptoms in childhood and adolescence.