We report the incidence, risk factor(s), and overall survival (OS) of second/multiple primary tumors (SPTs/MPTs) in oral cavity squamous cell carcinoma (OSCC) patients in betel quid chewing areas. Of 816 untreated OSCC patients who had radical surgery, 15.7% had either synchronous or metachronous SPTs. The SPTs (70.3%) were at the oral cavity. SPTs (18.8%) developed third primary tumors, with a significantly higher incidence in synchromous than metachronous SPTs (p=0.001). An optimal, but significantly lower, 5-year OS was observed in patients with SPTs/MPTs than without (54.0% vs. 67.2%, p=0.0195). By multivariate analyses, OSCC sub-sites (p=0.006) and lymphatic permeation (p=0.040) were independent risk factors for SPT rate. A significantly higher 5-year OS was observed in SPT patients receiving a second radical surgery at the oral cavity/soft palate than patients that did not (p=0.0001). A good survival rate can be obtained for OSCC patients with resectable SPTs/MPTs.