Abstract: Objective: To investigate the pathological characteristics and lymph node metastasis of carcinoma of the head of the pancreas and ampullary carcinoma. Methods: The pathological characteristics and lymph node metastasis of 201 patients with carcinoma of the pancreas and ampullary carcinoma were retrospectively analyzed and the chi-square test was conducted to analyze the relationship between lymph node metastasis and pathological factors. Results: A total of 201 cases with carcinoma of the head of the pancreas and ampullary carcinoma underwent pancreaticoduodenectomy. The rate of lymph node metastasis was 32.65% (16/49) in cases of carcinoma of the head of the pancreas and 30.92% (47/152) in cases of ampullary carcinoma, and the location of lymph node metastases was similar, with 88.89% (32/36) of the cases with solitary lymph node metastasis found in the pancreaticoduodenal region. The chi-square test revealed that lymph node metastasis of ampullary carcinoma was associated with the size of tumors (P=0.002), histological differentiation (P=0.012), duodenal infiltration (P=0.008), T stage (P=0.000), and pancreatic infiltration (P=0.005), but carcinoma of the head of the pancreas had no relation to the above pathological factors. However, the rate of neural infiltration was high in cases of carcinoma of the head of the pancreas. Conclusion: Pathological characteristics and lymph node metastasis of carcinoma of the head of the pancreas are different from those of ampullary carcinoma, so it follows that the treatments should be different from each other. Enlarged radical excision is needed for carcinoma of the head of the pancreas.