The neural cell adhesion molecule (N-CAM) is a group of cell surface glycoproteins involved in direct cell--cell adhesion. N-CAM expression in normal and neoplastic tissues was examined with specific antibodies and oligonucleotide probes by immunohistochemistry and in situ hybridization. Most neuroendocrine cells and tumors with secretory granules expressed N-CAM protein and mRNA. Parathyroid adenomas (4) were somewhat unusual, because N-CAM mRNA, but not protein, was detected in some of these benign neoplasms. Most non-neuroendocrine cells and tumors did not express N-CAM, although uterine smooth muscle and an adrenal cortical carcinoma were both positive. Western blots disclosed proteins of 180, 140, and 120 kd in normal adult brain, whereas two pheochromocytomas, a null cell adenoma, and a gastrinoma had proteins of approximately 180 and 140 kd. These results indicate that N-CAM protein and mRNA are widely expressed in neuroendocrine cells and neoplasms. N-CAM oligonucleotide probes as well as antibodies against N-CAM can be used as broad-spectrum neuroendocrine markers. In addition, these molecular probes can be used to examine the role of N-CAM in the development and regulation of neuroendocrine tissues.