There is a growing consensus that the neuropsychological underpinnings of developmental dyscalculia (DD) are a genetically determined disorder of 'number sense', a term denoting the ability to represent and manipulate numerical magnitude nonverbally on an internal number line. However, this spatially-oriented number line develops during elementary school and requires additional cognitive components including working memory and number symbolization (language). Thus, there may be children with familial-genetic DD with deficits limited to number sense and others with DD and comorbidities such as language delay, dyslexia, or attention-deficit-hyperactivity disorder. This duality is supported by epidemiological data indicating that two-thirds of children with DD have comorbid conditions while one-third have pure DD. Clinically, they differ according to their profile of arithmetic difficulties. fMRI studies indicate that parietal areas (important for number functions), and frontal regions (dominant for executive working memory and attention functions), are under-activated in children with DD. A four-step developmental model that allows prediction of different pathways for DD is presented. The core-system representation of numerical magnitude (cardinality; step 1) provides the meaning of 'number', a precondition to acquiring linguistic (step 2), and Arabic (step 3) number symbols, while a growing working memory enables neuroplastic development of an expanding mental number line during school years (step 4). Therapeutic and educational interventions can be drawn from this model.