Giant cell angiofibroma is a rare, soft tissue tumor that was first described in the orbit. Since then, several case reports have described this tumor in a number of extra-orbital sites, suggesting a wider anatomic distribution than is generally recognized. The tumor typically acts in a benign fashion with only rare local recurrences but no tendency to metastatic disease. Here, we report the first case of a giant cell angiofibroma in the oral cavity. The tumor presented as a soft tissue nodule on the buccal mucosa of a 60-year-old man. The histologic differential diagnosis included a number of other uncommon soft tissue neoplasms, including giant cell fibroblastoma, solitary fibrous tumor, and pleomorphic lipoma. The histologic and immunohistochemical features of this tumor and differentiation from other histologically similar soft tissue neoplasms are briefly discussed.