A 59-yr-old man with carcinoma of the stomach, concurrent acquired hyperkeratosis (tylosis) of the palms and soles, and acanthosis of the esophageal mucosa is reported. He presented the tylosis and esophageal lesions when the carcinoma was evident. Resection of the stomach resulted in diminution of the skin and esophageal lesions. The association of sporadic tylosis and carcinoma of the stomach is extremely rare. This is the first case report documenting the association of gastric cancer, tylosis, and acanthosis of the esophageal mucosa.