Neuroblastoma, a cancer of young children, is well known for its diverse pattern of presentation. Approximately one-half of children have localized tumors that can be cured with surgery alone. The remaining children have widespread metastatic disease or quite large, aggressive, localized tumors. These children have a poor long-term survival rate of approximately 30%. We review the prognostically significant histologic and molecular features of high risk neuroblastoma and propose an algorithm to dissect further the differentially expressed genes that define the phenotype of this disease. Over the past 25 years, much effort has gone into establishing reliable prognostic indicators of high risk disease. For neuroblastoma, age, stage, and histopathology have time and again correlated well with outcomes. Chromosomal number, or ploidy, and amplification of the MYCN oncogene have proved to be equally as important and are commonly used to stratify patient risk. Other potentially lucrative markers include chromosome 1p deletion, chromosome 17q gain, receptor tyrosine kinases A and B (trk-A, trk-B), CD44, CXCR4, and multidrug resistance associated protein (MRP). With the onset of new technology, expression microarrays are now being used to profile advanced-stage neuroblastoma on a larger scale. Genes particular to cell cycle control, DNA/RNA replication, ribosomal synthesis, neuronal differentiation, and intracellular/extracellular signal transduction have been identified through differential expression analysis. We present our research on the MYCN transcription factor and target gene, MCM7, to show the utility of this approach.