The existence of primary branchiogenic carcinoma is controversial. In 1950, Martin et al. established four criteria for the diagnosis of primary branchiogenic carcinoma. In 1989, Khafif et al. proposed new criteria, which are currently most recognized in the literature. A pathologic description of the surgical specimen is analyzed and compared with a critical review of the literature. A case is presented in which imaging established the diagnosis of a benign second branchial cleft cyst 2 years prior to the diagnosis of a branchiogenic carcinoma in the same cyst. This cyst was resected and was found to have squamous cell carcinoma arising from the benign epithelium. This case satisfies the histologic criteria established by Martin and Khafif for a primary branchiogenic carcinoma arising in a previously benign second branchial cleft cyst.