Neoplasms that arise in the peripheral (e.g., carotid body tumors, neuroblastomas, pheochromocytomas) or central (gangliocytomas, medulloblastomas) nervous system express a number of neuron-specific gene products. Presumably, these tumors are derived from precursor cells that are or have the potential to develop into neurons or neuron-like cells. This report provides a critical examination of the hypothesis that cytoskeletal proteins of normal neurons, in particular the neuron-specific class of intermediate filaments (neurofilaments), are present but are abnormal in neoplasms derived from neurons or neuron-like cells. The implications of these findings for understanding tumor promotion and progression, and for development of molecular probes for the diagnostic assessment of these neoplasms, are discussed.