Aggressive surgical resection is the preferred method of treatment for duodenal mesenchymal tumors. Intraoperatively, the malignancy of the tumor is judged according to the size of the tumor, local infiltration and metastasis, the degree of nuclear schizophrenia, the integrity of the envelope and whether it is combined with intratumoral necrosis. For duodenal mesenchymal tumors judged as benign or low malignancy and more than 1 cm from the duodenal papilla, local resection and partial resection of the intestine are feasible. Clinical studies have confirmed that the difference in efficacy between local resection and radical resection is not significant; therefore, local resection, especially for duodenal mesenchymal tumors, can avoid highly invasive and costly procedures such as pancreaticoduodenectomy. However, negative margins should be emphasized to avoid residual tumor or rupture. In our group, one case of recurrence and death 5 years after local resection was a case in the mid-1990s. Later, with increasing experience, better understanding of the disease and the application of intraoperative frozen section, there were no recurrence cases. For cases with intraoperative diagnosis of high malignancy or tumor close to the papilla, we advocate radical resection and do not routinely perform lymph node dissection unless the lymph nodes are obviously invaded. In this group, 7 cases of pancreaticoduodenectomy with or without pylorus preservation were performed with good results. For tumor diameter greater than 10 cm, postoperative Gleevec may be recommended to prevent recurrence. For patients with combined liver metastases, as long as possible, liver metastases should also be actively surgically resected to prolong survival time. In this group, one patient had a survival time of 3.5 years after resection of left liver metastases. In conclusion, the prognosis of duodenal mesenchymal tumor is better than that of gastrointestinal cancer, and complete surgical resection is the preferred method for its treatment.