Three patients with stage 4S neuroblastoma without MYC-N amplification who progressed to stage 4 with persistent liver involvement, were treated with iodine 131-meta-iodobenzylguanidine therapy, chemotherapy, and surgery. Successive histologic examination of the liver showed differentiation of the tumor in 2 patients and fibrosis in the third. One patient died of brain metastases at the age of 30 months. The other 2 patients are alive at 50 and 44 months. Diffuse liver involvement in patients with stage 4 progression of previous stage 4S without MYC-N amplification may differentiate after treatment. The aim of this report is to draw attention to major liver surgery that it may not be necessary in tumors without MYC-N amplification, despite the persistence of lesions in the liver.