We have retrospectively reviewed the treatment results of postoperative radiotherapy (RT) for advanced oral cavity cancers. The purpose of this study was to determine the impact of anatomic subsite on the results of treatment. Between 1975 and 1985, 51 patients with squamous cell carcinoma of the oral tongue (OT = 29 patients) and floor of mouth (FOM = 22 patients) were treated with combined surgery plus RT. All had an indication(s) for RT including advanced primary disease (T3 or T4) (29 patients), close or positive margins (34 patients), and multiple positive neck nodes and/or extracapsular extension (41 patients). With a median follow-up of 6 years, the 5-year actuarial local control rate was 74% and the rate of distant metastasis (DM) was 34%. Despite the similar T stage, margin status and median RT dose, the 5-year actuarial local failure rate was 38% for OT vs. 11% for FOM (ρ = 0.03). Furthermore, the median survival after recurrence was 9 months for OT and 40 months for FOM (ρ = 0.02). At 5 years the determinate survival for both sites was (55%), and the likelihood of developing a second malignancy was 31%. The likelihood of developing DM was 50% for FOM (NO-N1 = 3 of 12, N2-N3 = 8 of 10) and 21% for OT (NO-N1 = 4 of 21, N2-N3 = 1 of 8). This study highlights significant differences between FOM and OT cancers in response to combined surgery and RT. Future strategies should be directed at the enhancement of local control for OT and better systemic therapy for those with advanced N-stage FOM. Second primary cancers were an even greater threat to survival than anticipated.