N-myc is amplified between 5 and several hundred-fold frequently in neuroblastomas and, at lower frequency, in other human cancers with neuronal qualities, including retinoblastomas, gliomas, astrocytomas and small cell lung cancers. In neuroblastomas N-myc amplification is significantly correlated with poor prognosis; for other types of tumors such a correlation is difficult to make, due to low incidence of amplification. Amplification is associated with elevated expression, both of mRNA and protein. N-myc encodes two polypeptides of relative masses of 62 and 64 kDa, which are phosphorylated, at least in vitro, by casein kinase II and that are localized in the nucleus. There they can associate in vivo with another protein, Max, through a C-terminal dimerization motif, the leucine zipper. An N-terminal portion of N-myc, referred to as' Myc-boxes', can substitute for the transcription-activating function of the yeast transcription factor Gal 4, thus raising the possibility that N-myc itself may act as a transcription factor, either alone or in association with other factors.