A retrospective study of a group of 51 patients who underwent surgery for squamous cell carcinoma of the pyriform sinus was performed. Primary tumors and lymph nodes were reviewed histologically. The primary tumors were also examined by flow cytometry for DNA ploidy and cell cycle analysis. Sixteen (33%) of the cases were aneuploid and 64% had a moderate or high S-phase fraction. The overall 3-year survival rate was 49% (25/51). In the univariate analysis, tumor size, lymphatic invasion, inflammatory infiltrate, presence of lymph node metastases, clinical and histologic N status, size and number of lymph nodes involved, and presence of extracapsular extension all correlated with survival. When multivariate analysis was used, the only independent prognostic factors were tumor size, lymphatic invasion, and histologic N status. Ploidy and S-phase fraction did not contribute further prognostic information.