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This uncommon disease is characterized by rapid proliferation, high aggressiveness, and poor prognosis. To date, no standard treatment regimen has been established for this malignancy. The present study reported on a patient diagnosed with primary squamous cell carcinoma of the pancreas who showed recurrence after radical resection and adjuvant chemotherapy. The patient was refractory to salvage therapy with cytotoxic drugs, anti-angiogenesis drugs, and even immune checkpoint inhibitors, resulting in a poor prognosis. Notably, the Ki-67 proliferation index, a marker of tumor cell proliferation, increased from 40% in the surgical specimen to 80% in the recurrent tumor within 2 months. In addition, the literature on clinical characteristics as well as treatment options and their efficacy in patients with squamous cell carcinoma of the pancreas was reviewed and summarized to improve the understanding of the disease and treatment choices. 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