Congenital dental deficiency can lead to aesthetic and masticatory dysfunction, which have a great effect on the quality of life of patients. Genetic inheritance is the determining factor of congenital dental deficiency, which may follow the pattern of autosomal dominant, recessive, or sex chromosome inheritance. However, the specific genetic mechanisms are not clear. The prevalence of congenital absence of permanent teeth in the general population worldwide are not high, and familial oligodontia in clinically healthy patients is rare. This paper reported two cases of familial non-syndromic congenital teeth loss and included a review of literature referring to the etiology, clinical manifestations, and treatment of congenital dental deficiency.