A 60-year-old woman presented to hospital with abdominal pain and massive weight loss. Imaging studies confirmed the presence of a tumor of the pancreas. Histologic analysis of the sampling performed by echoendoscopic ultrasound fine-needle aspiration found aspects evocative of adenosquamous carcinoma. This case report highlights the difficulties of clinical pathologic diagnosis for these occasionally composite tumors. The patient underwent palliative chemotherapy based on platinum and 5-fluorouracil, followed by second-line chemotherapy with FOLFIRI after progression. Adenosquamous carcinoma of the pancreas remains a rare tumor with very poor prognosis and limited therapeutic options.