Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin that is associated with a high incidence of recurrence and metastasis. The thera peutic arsenal for this malignancy is limited and once it spreads, there is no e ffective treatment, c-kit expression has been demonstrated previously in primar y MCCs thus raising the possibility of treating MCCs with imatinib mesylate, the tyrosine kinase inhibitor that has shown promise in the management of c-kit ex pressing tumors. In this study we examine 25 additional primary MCCs and also 6 of their lymph node metastases. Formalin-fixed, paraffin-embedded tissues were stained immunohistochemically with an antibody directed against the KIT recepto r. Percentage and intensity of staining were analyzed semiquantitatively using a three-tiered system. Twenty-one of the 25 (84%) primary tumors stained posit ively for KIT, of which 14 (67%) showed widespread positivity. Five of the 6 ly mph nodes (83%) were similarly positive. High mitotic rate and vascular invasio n in the primary tumors tended to be associated with prominent staining in the l ymph node metastases. No association was found between c-kit expression and out come. We confirm that the majority of primary MCCs express c-kit and further fi nd that metastases are positive for the KIT receptor as well. Thus, c-kit expre ssion may be an early event in the transformation of MCC, but not a marker for t umor progression. Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin that is associated with a high incidence of recurrence and metastasis. The thera peutic arsenal for this malignancy is limited and once it spreads, there is no efective treatment, c-kit expression has been demonstrated previously in primar y MCCs thus raising the possibility of treating MCCs with imatinib mesylate, the tyrosine kinase inhibitor that has shown promise in the management of c-kit ex pressing tumors. In this study we examine 25 additional primary MCCs and also 6 of their lymph node metastases. Formalin-fixed, paraffin-embedded tissues were stained immunohistochemically with an antibody directed against the KIT receptacle r. Percentage and intensity of staining were analyzed semiquantitatively using a three-tiered system. Twenty-one of the 25 84%) primary tumors stained posit ively for KIT, of which 14 (67%) showed widespread positivity. Five of the 6 ly mph nodes (83%) were similarly positive. Hi gh mitotic rate and vascular invasio n in the primary tumors tended to be associated with prominent staining in the lymmph node metastases. No association was found between c-kit expression and out come. We confirm that the majority of primary MCCs express c-kit Thus, c-kit expre ssion may be an early event in the transformation of MCC, but not a marker for tumor progression.