Amplification and overexpression of cyclin D1 (CCND1) have been reported as independent prognostic indicators of several tumors. To investigate the association between CCND1 amplification and overexpression in oral squamous cell carcinomas (OSCCs), and to determine which is more reliable as a prognostic indicator, fluorescence in situ hybridization (FISH) on fine-needle aspiration (FNA) biopsies and immunohistochemistry were performed on 41 primary OSCCs (26 males, 15 females; mean age; 58.4 years, range 21-89 years). Thirteen patients were stage I, 13 were stage II, nine were stage III, and six were stage IV. CCND1 amplification and overexpression was detected in 13 (31.7%) and 27 (65.9%) of 41 cases. CCND1 was overexpressed in all cases showing CCND1 amplification. On the other hand, CCND1 overexpression was also detected in 14 of 28 cases (50.0%) lacked such amplification. Statistical analysis showed that the correlation between CCND1 overexpression and decreased survival just failed to reach statistical significance, and CCND1 amplification and nodal status were independent prognostic indicators. In conclusion, it will be necessary to investigate the other pathways that regulate CCND1 expression besides CCND1 amplification. From the present study, CCND1 amplification is a more reliable prognostic indicator than CCND1 overexpression in OSCCs.