Children with Velo-Cardio-Facial Syndrome (VCFS) consistently show mathematical disabilities (MD). At the neuropsychological level, it is important to know which general cognitive deficits underlie these MD. Therefore, we examined various mathematical abilities, working memory, rapid automatized naming and processing speed in 25 children with VCFS and 25 carefully selected matched controls. Children with VCFS showed a reduced ability to solve addition and subtraction problems and performed less accurately on multidigit arithmetic and word problem solving. There were no group differences on the general cognitive measures, except that children with VCFS performed higher than controls on the phonological loop tasks. To conclude, the administered general cognitive competencies could not give a satisfactory account of the MD in VCFS.