Benign osteoclast-like multinuclear giant cells are rarely found in tumors other than bone and soft tissue neoplasms, and they are even rarer in squamous cell carcinomas. We examined a nasopharyngeal tumor from a 52-year-old female who had undergone surgery one year earlier for hypopharyngeal squamous cell carcinoma. Histopathologically, in addition to tumor infiltration by atypical epithelial cells with squamoid differentiation, giant cells with 10-20 nuclei and a large amount of eosinophilic cytoplasm were seen infiltrating the tumor. The giant cells did not show atypia or mitosis. Immunohistochemically, the tumor cells stained for pan-keratin and epithelial membrane antigen, and the giant cells were positive for leukocyte common antigen, CD68, and Mac 387. This case was diagnosed as moderately differentiated squamous cell carcinoma with multinuclear giant cells. In this case, the giant cells infiltrating the tumor were benign and of monocytic/histiocytic origin. Studies including large case series are needed to obtain reliable information on the clinical and prognostic importance of this histological feature.