Chromoendoscopy with Lugol iodine staining provides important information on the development of squamous cell carcinoma (SCC). In particular, distinct iodine-unstained lesions (DIULs) larger than 10 mm show a high prevalence in high-grade intraepithelial neoplasia. It has also been reported that inactive ALDH2*1/*2 and less-active ADH1B*1/*1, and smoking, are risk factors for esophageal SCC. We previously examined telomere shortening in the esophageal epithelium of alcoholics, and suggested a high prevalence of chromosomal instability in such individuals. In the present study, we attempted to analyze telomere lengths in 52 DIULs with reference to both their size and multiplicity, ALDH2 and ADH1B genotypes, and smoking history. Patients with DIULs <10 mm (n = 42) had significantly longer telomeres than those with DIULs ≥10 mm (n = 10, p = 0.008). No significant differences in telomere length were recognized between the ALDH2 and ADH1B genotypes (ALDH2 active/inactive = 35/17, ADH1B active/inactive = 32/20; p = 0.563, 0.784, respectively) or among four groups of patients divided according to smoking history (never-, ex-, light, and heavy smokers = 3, 6, 21, and 22 patients, respectively; p = 0.956). Patients without multiple DIULs (n = 17) had significantly longer telomeres than patients with multiple DIULs (n = 35, p = 0.040). It is suggested that alcoholism reduces telomere length in the esophagus, irrespective of genotype or smoking habit. Telomere shortening may not generate cancer directly, but may create conditions under which SCC can develop more easily, depending on subsequent exposure to carcinogens.