The aim of this study was to determine the regional control rate with concurrent chemoradiotherapy (CRT) based on pretreatment nodal size in mucosal head and neck squamous cell carcinoma (HNSCC) in patients who achieved a complete response (CR) at the primary site by 12 weeks post-treatment. Between December 1997 and November 2003, 117 patients with node-positive HNSCC were treated with concurrent CRT, with 108 (92%) achieving a CR at the primary site by 12 weeks. There were 93 males (86%), median age 55 (37-79) years and the most common primary site was the oropharynx (65%). Patients were divided into three subgroups: <or=3.0 cm 70 (65%), 3.1-6.0 cm 30 (28%) and >or=6.1 cm 8 (7%). All patients received concurrent platinum-based chemotherapy and the median radiation dose was 70 Gy (60-72 Gy). The 3-year regional control rate based on pretreatment nodal size was <or=3.0 cm 88% (95% confidence interval (CI) 78-94%), 3.1-6.0 cm 72% (95%CI 49-86%) and >or=6.1 cm 50% (95%CI 15-77%) (P = 0.001). The 3-year regional control rate based on pre-treatment nodal size was <or=3.0 cm 88% (95%CI 78-94%), 3.1-6.0 cm 72% (95%CI 49-86%) and >or=6.1 cm 50% (95%CI 15-77%) (P = 0.001). These results provide a quantitative guide for the clinician as to the likelihood of regional control based on pretreatment nodal size following CRT in patients who achieve a CR at the primary site by 12 weeks post-treatment.