Merkel cell carcinoma is the cutaneous counterpart of small cell carcinoma, and the most important differential diagnosis is cutaneous metastasis of small cell carcinoma of the lung. There have been a handful of studies reporting on the utility of a variety of immunohistochemical markers that distinguish between the two entities. Achaete-scute complex-like 1 (MASH1, ASCL1) is important in the development of the brain and the diffuse neuroendocrine system including pulmonary neuroendocrine cells. A recent study, using a cDNA array, identified Mash1 as one of the best classifier genes to differentiate pulmonary small cell carcinoma from Merkel cell carcinoma. We immunohistochemically applied this finding to the diagnostic setting. A total of 30 cases of Merkel cell carcinoma and 59 cases of small cell carcinoma of the lung were immunostained with anti-MASH1 and TTF-1 antibodies. Of 59 small cell carcinomas, 49 (83%) expressed MASH1 in nuclear staining whereas out of 59 small cell carcinomas, 43 (73%) expressed TTF-1 in nuclear staining. MASH1 was completely negative in all 30 Merkel cell carcinomas whereas TTF-1 expression was seen in 1 of the 30 Merkel cell carcinomas (3%). MASH1 is a useful adjunct marker for differentiating small cell carcinoma of the lung from Merkel cell carcinoma.