The esophageal gland duct may serve as a pathway for the spread of early esophageal squamous cell neoplasia (ESCN) to a deeper layer. Deep intraductal tumor spreading cannot be completely eradicated by ablation therapy. However, the risk factors of ductal involvement (DI) in patients with ESCNs have yet to be investigated. We consecutively enrolled 160 early ESCNs, which were treated with endoscopic submucosal dissection. The resected specimens were reviewed for the number, morphology, resected margin, distribution and extension level of DI, which were then correlated to clinical factors. A total of 317 DIs (median:3, range 1-40 per-lesion) in 61 lesions (38.1%) were identified. Of these lesions, 14 have DIs maximally extended to the level of lamina propria mucosa, 17 to muscularis mucosae, and 30 to the submucosa. Multivariate logistic regression analysis showed that tumors located in the upper esophagus (OR = 2.93, 95% CI, 1.02-8.42), large tumor circumferential extension (OR = 5.39, 95% CI, 1.06-27.47), deep tumor invasion depth (OR = 4.12, 95% CI, 1.81-9.33) and numerous Lugol-voiding lesions in background esophageal mucosa (OR = 2.65, 95% CI, 1.10-6.37) were risk factors for DI. The maximally extended level of ducts involved were significantly correlated with the cancer invasion depth (P < 0.05). Notably, 245 (77%) of the involved ducts were located at the central-trisection of the lesions, and 52% of them (165/317) revealed dilatation of esophageal glandular ducts. Five (1.6%) of the involved ducts revealed cancer cell invasion through the glandular structures. In conclusion, DI is not uncommon in early ESCN and may be a major limitation of endoscopic ablation therapy.