The large variability (7% to 100%) in previously reported rates of receptor tyrosine kinase KIT expression in Merkel cell carcinoma (MCC) may be owing to the use of heat-induced epitope retrieval. High frequency of reported KIT reactivity by immunohistochemistry (IHC) in part prompted the initiation of a phase 2 clinical trial of imatinib mesylate (Gleevec, Novartis Pharmaceuticals, East Hanover, NJ) for the treatment of advanced MCC. Our experience has been that a small number of MCCs (12.5%) are positive for KIT by IHC. We also found a higher rate of apparently KIT-positive MCCs (75%) using heat-induced epitope retrieval. Our anecdotal experience with the use of imatinib mesylate has been disappointing. As IHC detection of KIT expression does not correlate with the presence of KIT-activating mutations, protein expression as tested by IHC should not be used to determine if patients would respond to imatinib mesylate. Indeed, our review of the literature and the apparent lack of efficacy of imatinib mesylate for MCC in a recent phase 2 trial suggest a minor role for KIT signaling in MCC tumorigenesis.