We report the histopathologic findings in 420 patients with stage III and IV neuroblastoma enrolled in Childrens Cancer Study Group trials conducted from 1980 to 1983. A prospective study of individual cytohistologic features showed that outcome was related in a statistically significant manner to mitotic rate, multi-nuclearity, foam cells, ganglion cells, necrosis, and calcification, but only the latter was consistent for both stages. A similar test of four selected published classifications indicated the greatest prognostic value for the system developed by Shimada et al to distinguish favorable from unfavorable tumors. This classification proved significant in both stages and on examination of both primary and metastatic sites. Concordance in histologic assignment of prognosis by two observers was 83%. We conclude that the Shimada classification is valid and reproducible, and that it may be useful in planning therapy in advanced neuroblastoma. Selected cytohistologic parameters and the other classifications were less strongly predictive of outcome, but are worthy of continued study.