Melanosis is frequently observed in the upper aerodigestive tract of Japanese alcoholic men, and the prevalences of squamous cell dysplasia and SCC in the upper aerodigestive tract of Japanese alcoholic men are high. This study evaluated associations between melanosis and both neoplasms of the upper aerodigestive tract and factors contributing to the development of melanosis in Japanese alcoholic men. Endoscopic screening of 643 Japanese alcoholic men (aged 50-79 years) was combined with oropharyngolaryngeal inspection and esophageal iodine staining, and ALDH2 genotyping was carried out in 425 of them. Melanosis was frequently (20.8%) observed in the upper aerodigestive tract. The palate was the most common site of melanosis (11.2%), followed by the pharynx (9.5%), and by the esophagus (7.0%). The incidence of melanosis was higher in those with esophageal dysplasia (31/126, 24.6%), esophageal SCC (19/42, 45.2%), and oropharyngolaryngeal SCC (8/14, 54.1%) than in cancer- and dysplasia-free controls (69/437, 15.8%). The presence of melanosis was associated with a higher risk of esophageal dysplasia, esophageal SCC, and oropharyngolaryngeal SCC (OR 1.69, 4.03, and 6.61, respectively). Multivariate analysis showed that older age, heavier smoking, and heterozygosity for inactive ALDH2 were positively associated with the presence of melanosis. The presence of melanosis indicates a high risk for neoplasms in the upper aerodigestive tract of Japanese alcoholic men. Melanosis and neoplasms have the same causes, including older age, heavy smoking, and high acetaldehyde exposure.