Epidermodysplasia verruciformis is a rare, multifactorial disorder. The disease has genetic and immunologic components. Many patients have impaired cell-mediated immunity. Although squamous cell cancers may develop in EV patients, the association with other hematological or solid malignancies and EV is reported in a few studies. In this report, a case of EV with primary mediastinal large B-cell lymphoma is presented. A 20-year-old man with a five years history of red-brown macular lesions was admitted to our hospital. The skin biopsy revealed epidermodysplasia verruciformis. Persistent cough started during the hospitalization. On the chest X-ray, mediastinal enlargement was determined. Thoracic computed tomography demonstrated a mediastinal mass of 6 cm in diameter. Diffuse, large B-cell lymphoma was diagnosed. The chemotherapy (R-CHOP regiment) and involved field radiotherapy were administered. Complete response was achieved after the combined treatment modality. He is lymphoma- free for 18 months follow-up. Epidermodysplasia verruciformis is frequently seen in immunosuppressive patients and many accompany infections with type human papilloma virus subtypes such as 5 and 8. These human papilloma virus subtypes that have oncogenic properties may trigger lymphomagenesis. In addition, lymphomas are seen more frequently in immunosuppressive patients than healthy persons. We conclude that there may be a predisposition to lymphoma development in epidermodysplasia verruciformis patients.