Context.-High-grade neuroendocrine carcinomas and carcinoids can arise in different sites such as lung, gastrointestinal tract, prostate, and skin. Classic neuroendocrine markers such as CD56, synaptophysin, and chromogranin cannot distinguish carcinoids from highgrade neuroendocrine carcinomas. Recently, mouse monoclonal mASH1 has been shown to help discriminate carcinoids from high-grade neuroendocrine carcinomas in various neoplastic sites. To date, there have been no comprehensive immunohistochemistry studies with mASH1 on nonneuroendocrine neoplasms. Objective.-To evaluate the specificity and sensitivity of mASH1 in various normal and neoplastic tissues, including lung cancers. Design.-Formalin-fixed, paraffin-embedded tissue microarrays consisting of normal tissues and various neoplastic tissues were immunohistochemically evaluated with mASH1. Results.-In normal tissues (n = 30), mASH1 (nuclear staining) was sparsely expressed in the molecular cell layer, white matter, and granular cell layer of cerebellum; C cells in thyroid; and epithelial cells in thymus. In lung cancers, mASH1 stained 1.1% (1 of 93) of adenocarcinomas, 0.9% (1 of 111) of squamous cell carcinomas, 0% (0 of 30) of large cell carcinomas, 66.7% (6 of 9) of large cell neuroendocrine carcinomas, and 82.5% (94 of 114) of small cell carcinomas. In various other neoplastic tissues (n = 1114), mASH1 was expressed in thyroid medullary carcinomas, thymic carcinomas, and brain cancers; mASH1 was also expressed in a very low percentage of breast carcinomas, ovarian cancers, and pancreatic neuroendocrine tumors. All typical carcinoids of various sites were negative (0 of 11), however, in lung atypical carcinoids, mASH1 was expressed in 42.9% (9 of 21). Conclusions.-Although not organ specific, mASH1 is highly specific for high-grade neuroendocrine carcinomas versus carcinoids and other nonneuroendocrine neoplasms.