Among primary cutaneous B-cell lymphomas, follicle center lymphomas represent, according to the World Health Organization-European Organisation For Research and Treatment of Cancer classification, a subgroup with a favorable prognosis. We describe the case of a 45-year-old man who presented with large infiltrated tumors and nodules coalescing into a wide ulcerated plaque of the scalp, extending from the frontal to the occipital region. At the vertex, 2 large ulcerations were present, reaching the subcutaneous tissues and the underlying bone structures with osseus infiltration and erosion and consequent meningeal exposure. A left retroauricular lymphadenopathy was also present. Histology and immunohystochemistry diagnosed a relapse of primary cutaneous follicle center lymphoma with multilobated histomorphology and lymph node involvement. The histological picture was unchanged from the first sample of 1989. Due to a refusal to treatment, the lesion progressively grew until now. After 6 courses of chemotherapy (cyclophosphamide, vincristine, liposomal doxorubicin, prednisone-Rituximab), the tumor displayed an impressive complete regression with the persistence of a 4-cm occipital ulceration and underlying bone erosion. The adenopathy disappeared as well. This case gave us the opportunity to observe the natural development of the disease, leading to local mutilating and destroying lesions but with low tendency to systemic spread and an impressive response to chemotherapy.