Programmatic, multidisciplinary research provided converging brain, genetic, and developmental support for evidence-based diagnoses of three specific learning disabilities based on hallmark phenotypes (behavioral expression of underlying genotypes) with treatment relevance: dysgraphia (impaired legible automatic letter writing, orthographic coding, and finger sequencing), dyslexia (impaired pseudoword reading, spelling, phonological and orthographic coding, rapid automatic naming, and executive functions; inhibition and rapid automatic switching), and oral and written language learning disability (same impairments as dyslexia plus morphological and syntactic coding and comprehension). Two case studies illustrate how these differential diagnoses can be made within a conceptual framework of a working memory architecture and generate treatment plans that transformed treatment nonresponders into treatment responders. Findings are discussed in reference to the importance of (a) considering individual differences (diagnosis of impaired hallmark phenotypes) in planning and evaluating response to instruction and modifying instruction when a student is not responding; (b) recognizing that teaching may change epigenetic gene expression at one stage of schooling, but not the underlying gene sequences that render individuals still vulnerable as curriculum requirements increase in nature, complexity, and volume in the upper grades; and (c) using evidence-based diagnoses of specific learning disabilities that are consistent across states for free and appropriate education K to 12 and for accommodations throughout higher education and professional credentialing.