Background Inflammatory linear verrucous epidermal nevus (ILVEN) is a rare type of epidermal nevus that occurs in infancy and develops along Blaschko’s lines. Due to its rarity and clinical/histological similarities with other cutaneous disorders, correct diagnosis is sometimes difficult. In the present case, the whole exome sequencing of blood found no germline mutation, but the sequencing of the biopsy specimen revealed a novel potential pathogenic somatic mutation, C > T at rs200881715 (p.R698X) in the cspp1 gene, which may provide new insight into the mechanism of ILVEN.Patient concerns A 10-year-old girl presented with linear, pruritic, erythematous, scaly, and exophytic verrucous skin lesions on her left thigh, buttock, and hand unilaterally along Blaschko’s lines from the third day after birth. Diagnosis Biopsy revealed psoriasiform acanthosis, papillary hyperplasia with orthohyperkeratosis, and parakeratosis of squamous epithelium, which are histological characteristics of ILVEN. Interventions Owing to the large lesion size and significant refractory response to previous treatments, multiple-stage surgical resections with a tissue expander were performed. Outcomes After surgical resection and defect reconstruction with a tissue expander, the outcome was satisfactory for the patient and her family. No recurrence was detected during the follow-up visits. Conclusion ILVEN is a rare type of cutaneous hyperplastic disease, and treatment is extremely challenging. Biopsy should be performed at the diagnostician’s discretion or if refractory to conservative treatments. Timely diagnosis and surgical intervention could result in satisfactory outcomes.