Development of a second primary tumor (SPT)contributes to a poor prognosis, even if the primary oral tumor (OT) was adequately managed. SPT develops as synchronous or metachronous esophageal cancers in 1-20% patients with oral squamous cell carcinoma (OSCC). This study aimed to evaluate the prevalence and associated factors for SPT of the upper digestive tract in 80 Japanese patients with OT (OSCC, oral intraepithelial neoplasia/carcinoma in situ : OIN/CIS, and verrucous carcinoma : VC). SPT were detected in 67 patients, 8 with esophageal carcinoma (EC), 2 with intraepithelial neoplasia (IN), 3 with gastric carcinoma (GC), 7 with epithelial dysplasia (ED), and 47 with other diseases. Malignant tumors (EC, IN, GC), were detected in 13/80 patients (16.3%). Univariate analysis showed that Brinkman index (BI) was a candidate associated factor. In the multivariate analysis, BI as a continuous variable was also a significant associated factor. We strongly suggest that endoscopic screening be performed to identify malignancies of the upper digestive tract in patients with OSCC, OIN/CIS and VC.