Epidermolysis bullosa simplex with mottled pigmentation (EBS-MP) is an autosomal dominant disease characterized by nonscarring blistering after minor trauma, reticulated pigmentation, and palmoplantar hyperkeratosis. EBS-MP is caused by a mutation in the KRT5 or KRT14 gene encoding the keratinocyte intermediate filament. A 14-year-old girl presented with reticulated hyperpigmentation of the trunk and both extremities, which was observed 9 years ago. Additionally, punctate hyperkeratotic papules were observed on both the palms and soles. She had a history of being diagnosed with EBS as a baby. Skin biopsies were performed on both the hyperpigmented and hyperkeratotic papules. Based on the clinical and histopathological findings, the patient was diagnosed with EBS-MP, and next-generation sequencing was performed. Genetic screening identified a p.P25L mutation in the KRT5 gene. Herein, we report a case of p.P25L mutation in the KRT5 gene in a patient with EBS-MP.