We evaluated the risk of development of a second primary cancer in 669 patients diagnosed with cancers of the mouth and meso-hypo pharynx at Osaka Medical Center for Cancer and Cardiovascular Diseases. During 1978-93, 70 of the patients developed a second primary cancer, yielding on observed to expected ratio (O/E) of 2.92 [95% confidence interval (CI) = 2.27-3.69]. Significant excess risk was noted for cancers of mouth and pharynx (O/E = 12.01, 95% CI = 3.87-28.04), esophagus (O/E = 25.22, 95% CI = 14.94-39.86), colon (O/E = 3.85, 95% CI = 1.41-8.39), larynx (O/E = 9.93, 95% CI = 2.00-29.02) and lung (O/E = 2.58, 95% CI = 1.24-4.75). The risks of esophageal cancer and colon cancer were significantly elevated after five years had elapsed from the initial cancer diagnoses. The risk of cancers of the oral cavity, pharynx, larynx and esophagus in patients who had a history of current smoking without current daily drinking at the initial diagnosis was elevated past one year after the initial diagnosis (less than 20 cigarettes/ day; O/E = 12.50, 95% CI = 0.16-69.55, 20 cigarettes or more; O/E = 10.00, 95% CI = 1.12-36.10). The risk of cancers of the oral cavity, pharynx, larynx and esophagus in patients who had a history of current smoking with current daily drinking at the initial diagnosis was around two times higher than those who had a history of current smoking without current daily drinking (less than 20 cigarettes/day; O/E = 20.00, 95% CI = 2.25-72.21, 20 cigarettes or more; O/ E = 19.51, 95% CI = 8.40-38.45).