The hypodontia of a permanent tooth from a dental group represents a normal evolution in human dentition morphology. Nevertheless, the hypodontia of two teeth within a dental group is a rare developmental anomaly when not associated to a systemic syndrome. The aim of this study was to report two rare cases of four maxillary premolars hypodontia, not including the third molar, of two white women from the same family. There were presented clinical, radiological and genetic findings. These cases are of interest to practitioners for four aspects: the atypical phenotype of hypodontia, the complexity of craniofacial morphological changes, the autosomal dominant familial inheritance with variable expressivity and the difficult classification of diagnosis.