A carcinoma arising in the skin of the lip metastasized to the lymph nodes in the neck of a 53-year-old white man. Electron microscopy of the initial excisional biopsy specimen revealed that the tumor cells contained dense-cored vesicles (100 nm in diameter) in their cytoplasm and were joined by simple junctions. Cells from the nodal metastases were found to be immunoreactive for neuronspecific enolase, keratin intermediate filaments, and chromogranin A, but not for neurofilaments. The tumor was thus classified as a neuroendocrine skin carcinoma. In addition, its metastatic cells shared immunoreactive and ultrastructural characteristics of Merkel cells, which are situated in the basal epidermis of normal skin. Primary cultures from a nodal metastasis were established and characterized. The cells attached and proliferated on culture flask surfaces. The population-doubling time was 2 days. This is the first report where cells from a neuroendocrine skin carcinoma have been demonstrated to retain their characteristic ultrastructure in an in vitro environment (10 days). Studies of cells cultured from neuroendocrine skin carcinomas may prove useful in understanding the pathobiology of this disease and help define the in vitro growth requirements of nontransformed Merkel cells as well.