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We describe a case of an HPV+ tonsillar SCC in a 77\u2010year\u2010old male, with metastasis to the neck skin. This case is unique because of prominent in situ epidermal involvement on skin biopsy specimen, complicating the distinction between primary and secondary disease. The nature of the lesion was resolved using next\u2010generation sequencing of both the primary oropharyngeal SCC and skin lesion biopsy specimens. Both tumors showed identical <jats:italic>ATR<\/jats:italic> D1639G somatic mutations, while the skin lesion contained an additional <jats:italic>POLE<\/jats:italic> F1366L mutation. Clonal evolution of metastatic lesions is a well\u2010described phenomenon; comparing the genetic profiles of primary and metastatic specimens can be useful in evaluating the tumor origin as well as identifying targetable genetic aberrations.<\/jats:p>","DOI":"10.1111\/cup.14108","type":"journal-article","created":{"date-parts":[[2021,7,24]],"date-time":"2021-07-24T10:20:17Z","timestamp":1627122017000},"page":"1514-1519","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epidermotropic metastasis of squamous cell carcinoma of the tonsil: A case report with molecular confirmation"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4784-1977","authenticated-orcid":false,"given":"Philippa","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pathology Yale School of Medicine  New Haven Connecticut 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