BACKGROUND AND PURPOSE: : Intensity modulated radiation therapy (IMRT) combined treatment approaches, surgical and radiodiagnostic advances, respectively, lead to improved local-regional control in head neck cancer (HNC). With increasing local-regional control, distant metastases (DM) become more meaningful. In some trials without concomitant chemotherapy, induction chemotherapy (IC) resulted in an absolute reduction of DM by ~10-15%. In order to define a more efficient selection of patients at risk for DM with respect to IC and M-staging, we analysed our patients treated by contemporary standards. PATIENTS AND METHODS: : Between 1/2002 to 12/2007, 409 HNC patients were treated with IMRT; 303/409 (74%) underwent definitive, 106 (26%) postoperative IMRT. The mean/median follow-up was 23/20 months (3-72). 70% tolerated 4-7, 9% 1-3 cycles of simultaneous cisplatin. Treatment followed a prospectively designed protocol. In a previous study with 172 HNC IMRT patients, gross tumor volume (GTV) was found the strongest predictor for local-regional control. In the current study, this criterion has been prospectively tested for DM. Numbers needed to treat were calculated for IC. RESULTS: : DM developed in 28/399 (7%) patients; 10 presented initially with DM (total 38/409). In 13/28 (46%), DM remained the only manifestation of disease. GTV was the strongest predictor for DM (p < 0.0001) of all tested. Only 4% of patients with GTV < 70 cc developed DM, vs. 25% (18/73) with > 70 cc; only 6 of them (6/73, 8%) developed isolated DM. CONCLUSION: : GTV was the most significant predictor for DM, that could guide selective pre-treatment M-staging. The subgroup with isolated DM in the high risk group, that could benefit from IC, is small.