Objective To investigate the clinical features and genetic diagnosis of Leopard syndrome. Methods The clinical data, physical examination, assistant examination, and genetic screening of 1 case of Leopard syndrome were analyzed and relevant literature was reviewed. Results An 18-year-old Chinese Han male was admitted due to precordial discomfort after hard work. Physical examination showed that the development was normal and diverse lentigines were found over the face, body, limbs, palms, and soles. Ocular distance was at the upper limit of the normal range. Systolic murmur of grade 3/6 was heard in precordial area. Hearing and gonad examination showed no abnormality. ECG and Holter revealed complete right bundle branch block. Cardiac echocardiography, catheterization, and magnetic resonance confirmed left hypertrophic cardiomyopathy with the stenosis of right ventricular outflow tract. Hereditary screening showed that a heterozygous missense mutation of Tyr279Cys in exon 7 of the protein-tyrosine phosphatase non-receptor type 11 (PTPN11) gene was found, but no mutation was found in his parents. Conclusion Results of the study show that this sporadic Chinese Han case of Leopard syndrome is caused by the heterozygous missense mutation of Tyr279Cys of PTPN11 gene.