The alpha subunit of guanine nucleotide-binding protein Go (Go alpha), which was initially isolated from bovine brain, interacts with muscarinic cholinergic receptors and regulates neuronal calcium channels. Go alpha is known to be localized in neural tissues, some endocrine cells, and neuroendocrine tumors. We have immunohistochemically investigated the expression of Go alpha in 4 cases of Merkel cell carcinoma using the method of microwave treatment. In all cases of Merkel cell carcinoma, Go alpha was consistently detected on the plasma membrane and cytoplasm of the tumor cells. Nerve fibers in the skin were also positive for Go alpha, but other epidermal or dermal components such as keratinocytes, melanocytes, fibroblasts, or lymphoid cells were negative. Tumor cells of squamous cell carcinoma, cutaneous lymphoma, sweat gland carcinoma, and malignant melanoma were negative for Go alpha. The present study indicates that Go alpha may be a useful immunohistochemical marker of Merkel cell carcinoma.