This study investigates the role of carcinogen exposure in oral squamous cell carcinoma (OSCC) across different oral cavity sites. A retrospective analysis of 519 patients with primary OSCC at Helsinki University Hospital, Finland, between January 2016 and December 2020, was conducted. The study found that tumors were most commonly located in the tongue (51%), followed by the gingiva (21%) and floor of the mouth (FOM; 15%). FOM had significantly higher odds of a history of smoking and alcohol use compared to other sites (OR=25.78; 95% CI: 8.02–82.95; p<0.001). Gingival and buccal sites showed significantly lower associations with smoking and alcohol use. Older age was associated with a reduced likelihood of a history of smoking and alcohol use. Larger tumor size and FOM increased the odds for a history of smoking and alcohol use. The study concludes that OSCC of different oral cavity sites have notable differences in etiology, with FOM being almost exclusively related to conventional smoking and heavy alcohol use.This study investigates the role of carcinogen exposure in oral squamous cell carcinoma (OSCC) across different oral cavity sites. A retrospective analysis of 519 patients with primary OSCC at Helsinki University Hospital, Finland, between January 2016 and December 2020, was conducted. The study found that tumors were most commonly located in the tongue (51%), followed by the gingiva (21%) and floor of the mouth (FOM; 15%). FOM had significantly higher odds of a history of smoking and alcohol use compared to other sites (OR=25.78; 95% CI: 8.02–82.95; p<0.001). Gingival and buccal sites showed significantly lower associations with smoking and alcohol use. Older age was associated with a reduced likelihood of a history of smoking and alcohol use. Larger tumor size and FOM increased the odds for a history of smoking and alcohol use. The study concludes that OSCC of different oral cavity sites have notable differences in etiology, with FOM being almost exclusively related to conventional smoking and heavy alcohol use.