Background <p>Large cell neuroendocrine carcinoma (LCNEC) arising from the extrahepatic bile duct is a highly uncommon and aggressive malignancy. Due to the absence of an established standard and a lack of detailed reports on effective chemotherapy for recurrent biliary LCNEC, we present a case that demonstrated a temporary response to cisplatin and etoposide.</p> Case presentation <p>A Japanese man in his 70&#xa0;s presented with jaundice and weight loss. Imaging studies identified a tumor in the distal bile duct, and a biopsy of the bile duct confirmed a neuroendocrine tumor. The patient underwent a radical pancreaticoduodenectomy with regional lymph node dissection. Histopathology confirmed LCNEC with a Ki-67 index of 60% and metastases in the regional lymph nodes. Despite the initial surgical treatment, multiple liver metastases appeared 3&#xa0;months after surgery. Systemic chemotherapy using cisplatin and etoposide was initiated and produced a short-term partial response. However, after six cycles, the disease progressed, and subsequent therapy with amrubicin was ineffective. The patient passed away 14&#xa0;months after the operation.</p> Conclusions <p>This case underscores the aggressive behavior of biliary LCNEC and the limited success of current treatments. To our knowledge, this is the first reported case of biliary LCNEC with recurrent liver metastases demonstrating a radiologically confirmed partial response to cisplatin and etoposide therapy. A review of previously published cases revealed comparable outcomes, underscoring the need for further investigation to develop effective therapeutic strategies for LCNEC of the extrahepatic bile duct.</p>