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We performed immunohistochemical, ultrastructural, terminal deoxynucleotidyl transferase–mediated dUTP-biotin nick-end labeling (TUNEL), and DNA ladder studies of apoptosis in nine cases of Merkel cell carcinoma (MCC). None of the cases showed spontaneous regression as has been reported in several MCCs. Neuron-specific enolase was demonstrated by immunohistochemistry (8/8 MCCs), and staining for cytokeratin 20 was positive (2/8 MCCs). Ultrastructural examination revealed many cytoplasmic dense-cored granules, desmosome-like structures, and intermediate filaments. The granules were seen along the plasma membrane or around perinuclear centrioles. We found various stages of development of apoptotic bodies. Apoptosis resulted in vacuolization and fragmentation of nuclei and phagocytosed bodies in tumor cells. Apoptotic cells were also detected by TUNEL, DNA ladder, and immunostaining using the antibody against Fas (Apo-1/CD95) antigen. It seems that a high apoptotic rate is a common finding in MCC, although spontaneous regression is an exceedingly rare event. It is thus unlikely that apoptosis alone would explain spontaneous regression.