Background: This study was conducted to describe the frequency and significance of squamous cells in fine needle aspiration (FNA) specimens of the pancreas in benign and malignant processes. Methods: A retrospective review was performed of 102 patients with squamous cells in their pancreatic FNA specimens from 1986 to 2012. The malignant cases were classified as adenosquamous carcinoma (ASqC) or metastatic squamous cell carcinoma, and a double institutional review of the ASqC cases was undertaken to characterize the clinical and pathological features and survival statistics of patients who present with unresectable or metastatic ASqC and have no follow-up surgery. Survival analyses were performed. Results: Of the 4,094 pancreas FNA procedures performed in the study, squamous features were found in 102 (2.5%) of all cases, and 48% of these cases represented ASqC. The other cases were contamination (52%) or atypical (<1%). ASqC constituted 4.5% (46/1,025) of all primary pancreatic exocrine malignancies. When compared with conventional adenocarcinoma, ASqC demonstrated a significantly poorer overall median survival (11.0 vs. 6.51 months; p = 0.023), and this difference was also seen in patients presenting with metastatic disease (median survival of 9.1 vs. 4.2 months; p = 0.025). Conclusions: Squamous cells in FNA specimens from the pancreas have a broad differential diagnosis that ranges from contamination to ASqC.