Oral squamous cell carcinoma (OSCC) in Asians is highly associated with the abuse of areca (betel) chewing. There are several hundred million Asians who chew areca and are therefore at high risk of OSCC. Aberrance in cyclin D1 (CCND1) and/or cortactin (CTTN), which are localized on 11q13, seems to be critical events for the development of oral carcinogenesis. This study identified amplifications of CCND1 and CTTN by quantitative (Q)-PCR analysis in 50% and 45% of OSCC samples, respectively. Co-amplification of both genes was identified in 20% of tumors. Higher CTTN expression was associated with nodal metastasis of the OSCC, while the amplification of CCND1 was identified in 28% of oral brushed samples from areca chewers, who form a high risk group for OSCC. This study confirms the importance of alterations in CCND1 and CTTN with respect to areca-associated OSCC, and demonstrates that there is an early occurrence of amplification of these genes in the risk population. The non-invasive brushing sampling method coupling with Q-PCR analysis needs to be validated for use as an early detection system for gene copy changes, which should aid oral cancer prevention.