Neuroblastoma describes a cancer of the developing, immature neural cells found in the embryo or fetus, called neuroblasts. This condition was first described in 1864 by the German physician Rudolf Virchow who called the tumors he found in the abdomens of children gliomas.

In 1910, James Homer Wright noted that these tumors originated from in an immature, primitive form of neural cell and he therefore named the tumors neuroblasts, as "blastoma" refers to a collection of immature, undifferentiated cells. Wright also documented the formation of round clumps of cells in samples of bone marrow and these are now commonly referred to as "Homer-Wright pseudorosettes."It was in 1891 that German pathologist Felix Marchand first noted the features of the tumors developing in the sympathetic nervous system and the adrenal medulla that lies over the kidneys. Stage four (4S) neuroblastoma, which is characterized by spread to the liver but not the bone was described by William Pepper in 1901.

In 1914, Herxheimer went on to show that within the tumors of neuroblastomas, special silver stains could highlight the neuronal fibrils allowing the cancer to be visualized under the microscope.

In 1927, Cushing and Wolbach found that not all neuroblastomas were cancerous and while some were malignant and spread rapidly to various organs in the body such as the liver, skin, bone and bone marrow, others resolved independently of treatment.

In some rare cases, they found that the tumors turned into non-malignant or benign masses called ganglioneuromas, which may also resolve on their own. Everson and Cole added that the transformation from cancerous to non-cancerous forms was rare in babies over 6 months of age.

In 1957 Mason discovered that the presence of catecholamines could be detected in the urine of children with neuroblastoma. Cathecholamines are hormones that are produced in high quantities by the tumors, providing a marker for presence of the illness.