OBJECTIVES: To evaluate treatment-related toxicities among patients with squamous cell carcinoma of the head and neck (SCCHN) treated in real-world clinical practices. METHODS: We used a population-based tumor registry at a large, US health system, to identify all cases of stage III or IV SCCHN diagnosed from 2000 to 2006. We identified the incidence/severity of acute and late toxicities associated with SCCHN treatment from detailed medical record reviews. Acute and late toxicities were evaluated using CTCAE3 criteria and RTOG/EORTC late radiation morbidity scoring scheme, respectively. The incidence and severity of toxicities are presented by treatments. Detailed analyses according to tumor stage and location, grade, and acute versus late events were examined. RESULTS: We identified 195 patients with SCCHN: A total of 104 patients (53%) received chemotherapy (chemo) + radiation therapy (RT); 87 (45%) received RT only; four patients (2%) received chemotherapy only or other/no treatment.  Adverse Events of Interest (grade 2-4) by Treatment Received (N=191*): Gastrointestinal: 160 (83.8), 89 (85.6), 71 (81.6); Xerostomia: 61 (31.9), 41 (39.4), 20 (23.0); Dysphagia: 70 (36.6), 44 (42.3), 26 (29.9); Dermatology: 91 (47.6), 54 (51.9), 37 (42.5); Pulmonary: 74 (38.79), 41 (39.4), 33 (37.9); Aspiration pneumonia: 62 (32.5), 37 (35.6), 25 (28.7); Dehydration: 43 (22.5), 29 (27.9), 14 (16.1); Subcutaneous tissue: 30 (15.7), 18 (17.3), 12 (13.8); Infection: 29 (15.2), 21 (20.2), 8 (9.2); Renal/Genitourinary: 19 (9.9), 14 (13.5), 5 (5.7); Auditory: 16 (8.4), 12 (11.5), 4 (4.6); Bone: 4 (2.1), 3 (2.9), 1 (1.1) for Total n=191 n(%), Chemo+RT n=104 n(%), RT only n=87 n(%). Note: Four patients received chemotherapy only or other/no treatment. CONCLUSIONS: Treatment-related toxicity in patients with advanced SCCHN is common. The addition of chemotherapy to radiation is associated with increased risk treatment-related toxicities. These data provide real-world incidence rates of toxicity as observed in clinical practice.