The aim of this study was to explore the patterns of tooth agenesis in Japanese orthodontic patients with bilateral agenesis of mandibular second premolars. A total of 80 Japanese orthodontic patients with 2 congenitally missing mandibular second premolars were selected as the subjects of this study (experimental group). Another 80 individuals without bilateral agenesis of mandibular second premolars were collected for comparison (control group). The 2 groups were matched with regard to sex. Radiographs, dental casts and records of medical and/or dental treatment were used to identify tooth agenesis. The Chi-square test, odds ratio, and test for equality were used to make statistical comparisons. The prevalence rates of other types of tooth agenesis were significantly higher in the experimental group than in the control group. The occurrence of agenesis of maxillary and mandibular lateral incisors and third molars, and maxillary second premolars was also significantly higher in the experimental group than in the control group. Significantly increased prevalence rates of symmetrical tooth agenesis, with third molars included, and oligodontia were observed in the experimental group. Japanese subjects with bilateral agenesis of mandibular second premolars are at significantly high risk of agenesis of other types of permanent teeth, symmetrical tooth agenesis and oligodontia.