We present a case of a 5-year-old boy with premature exfoliation of primary teeth. All eight primary incisors had exfoliated by the age of 3 years, and three canines and one primary first molar were subsequently lost when he was 4 years old. None of the exfoliated teeth exhibited caries. The boy also showed characteristic facial changes, tapering of the fingers, and mental and motor retardation. Based on these findings, he was diagnosed as having Coffin–Lowry syndrome. Premature exfoliation of primary teeth in Coffin–Lowry syndrome has been described in a few reports. This manifestation of the disease would be helpful for diagnosis at an early stage as those previous reports suggested.