Background and study aims: Endoscopic mucosal resection (EMR) has been applied to the treatment of superficial esophageal squamous cell carcinoma (SCC). The incidence and characteristics of metachronous multiple esophageal SCCs and Lugol-voiding lesions (LVLs) were investigated in a retrospective study in patients who had undergone EMR for superficial esophageal SCC. Patients and methods: 96 patients with esophageal SCC who had been treated by EMIR were followed up by endoscopy for 12 months or longer. Clinicopathologic parameters such as tumor size and location and presence of LVLs were examined. Results: 10 patients (10%) had synchronous multiple SCCs, and 12 (13%) developed metachronous multiple SCCs. The mean annual incidence of newly diagnosed tumor was 4.4%. The incidence of a speckled pattern of LVLs was 20/74 (27%) in patients with solitary SCC, 5/10 (50%) in synchronous multiple SCC, and 10/12 (83%) in metachronous multiple SCC. The incidence of the presence of speckled pattern of LVLs was significantly higher in patients with multiple SCCs than in those with solitary SCC (68% vs. 27%, P = 0.0004). Conclusions: Patients who have undergone EMR for esophageal SCC, especially those with metachronous multiple LVLs in the background mucosa, should undergo follow-up with close endoscopic observation using Lugol staining.