Ha-ras p21 expression and N-myc gene amplification were examined in 69 neuroblastomas and their clinical significance was analyzed retrospectively. Thirty-nine (89%) of forty-four patients who survived for more than 2 years after diagnosis showed high Ha-ras p21 expression, whereas 19 (76%) of 25 patients who died of progressive disease showed low Ha-ras p21 expression in their tumors. Although all 14 patients whose tumors exhibited N-myc gene amplification died of the disease, 11 other patients (56%) who died did not exhibit N-myc gene amplification. When we considered both low Ha-ras p21 expression and N-myc gene amplification as risk factors, 23 (92%) of the 25 patients who died had at least one of the two and thus could have been predicted to be high-risk patients at diagnosis. The combined analysis of the two factors should provide more accurate information pertinent to patient care.