Spontaneous maturation of Stage IVS neuroblastoma has been postulated as a mechanism for its favorable prognosis, but this has rarely been documented pathologically. We report on a patient with congenital Stage IVS neuroblastoma who had extensive subcutaneous and bone-marrow involvement. Serial photographs, biopsies, and vanillomandelic acid determinations documented the tumor's initial progression which was followed by spontaneous maturation and involution of the patient's disease over a 6-year period. No cytotoxic therapy was administered. Favorable biologic prognostic factors were documented, including tumor DNA and protein analyses for N-myc amplification or overexpression and analysis for serum neuron-specific enolase and ferritin. Implications for management and therapy of Stage IVS neuroblastoma are discussed with reference to this case and the recent literature.