During human evolution there has been an increase in the size of the brain and the cranium, whereas the size of the face, as well as the size and number of teeth have decreased. In modern humans, the occurrence of missing permanent teeth, namely tooth agenesis, is common. It could be attributed to a biological mechanism of tooth number reduction that has evolved during time and might still be active. Although, if evident, it would add support to this theory, the relationship between this phenotype and craniofacial size remains largely unknown. The present case-control study shows that modern individuals with tooth agenesis have indeed smaller facial configurations. For example, a 15-year-old female with no, one, or ten missing teeth would have a facial centroid size of 511.83, 510.81, or 501.70 mm, respectively. No such effect was observable in the cranial base and the cranium. Our results suggest that common gene regulatory mechanisms that have evolved over time, continue to regulate the number of teeth and facial size of modern humans in a coordinated manner. We anticipate our findings to enrich our understanding of the evolution and development of the human head and kindle future developmental research on this field.