It has been suggested that mathematical disabilities (MD) emerge as a consequence of impairments in basic number processing skills. The aim of the present study was to investigate basic number processing skills in children with Velo-Cardio-Facial Syndrome (VCFS), a common genetic disorder with a high prevalence of MD, and to examine whether these basic low-level skills account for their performance in single-digit arithmetic. Twenty-five children with VCFS and 25 individually matched controls (age range: 6-12 years) participated. They all completed two basic number processing tasks (number reading, number comparison) and three single-digit arithmetic tasks comprising addition, subtraction and multiplication. In the latter tasks, strategy use was recorded next to accuracy and speed. Our data revealed that children with VCFS were significantly slower than controls on number comparison but not on number reading. Analysis of the single-digit arithmetic data revealed that children with VCFS performed more poorly than controls on large addition and subtraction problems. Both groups did not differ on multiplication and small additions and subtractions. At the strategy level, children with VCFS were significantly slower in executing backup strategies in addition and subtraction, but showed preserved retrieval of arithmetic facts. Taken together, children with VCFS show a consistent pattern of deficits at the level of number representations, arithmetic operations and strategy use, which suggests an impaired quantity subsystem in terms of Dehaene et al.'s model (2003). Most importantly, the correlational analyses showed that basic number processing skills directly accounted for single-digit arithmetic performance and strategy use in the children of the present study.