AbstractWe aimed to clarify the differences in therapeutic outcomes of patients with pure undifferentiated-type and mixed undifferentiated-type cancers who underwent endoscopic submucosal dissection (ESD), and whether pre-treatment diagnosis of mixed undifferentiated-type cancer is associated with requiring additional surgery after ESD. Patients subjected to ESD as initial treatment between May 2005 and March 2017 were enrolled. There were 277 undifferentiated-type cancers (265 patients). Histologically, 258 lesions were pure-type and 19 were mixed-type. We compared therapeutic outcomes and pre-treatment factors (tumour diameter, tumour depth, ulcerative findings, tumour location, and the macroscopic, and histological type of the biopsy specimen) between pure-type and mixed-type lesions, and between cases not requiring additional surgeries and cases requiring additional surgeries. Tumour diameter >20 mm, submucosal invasion, and the presence of ulcerative findings made pre-treatment diagnosis more difficult for mixed-type than for pure-type lesions. In cases requiring additional surgery, pre-treatment diagnosis of mixed-type lesions was significantly more likely than pre-treatment diagnosis of pure-type lesions. For mixed-type lesions, pre-treatment histological diagnosis and careful consideration are necessary to determine indications for ESD to avoid additional surgery after ESD.