Some neuroblastoma tumors when cultured in vitro give rise to N (neuronal) and S (non-neuronal) cells, which differ in morphology, state of differentiation, and tumorigenicity. Previously, tumor-forming potential was shown to be characteristic of N cells but not S cells. We examined cultures of N and S cells derived from a well-characterized, N-myc-amplified human neuroblastoma cell line, NBL-W, to determine whether these N and S cells also show differential tumorigenicity in nude mice. N cells formed tumors in 94% of trials and S cells formed tumors in 56% of trials. Although S cell tumors had a longer lag phase prior to tumor development, when tumors developed, both N and S cell-derived tumors grew rapidly. These results suggest that S cells do not always represent a benign component of neuroblastomas.