This study is to determine the impact of virus in surgical outcomes among patients of head and neck cancer with N3 lymph node metastasis. A retrospective analysis was conducted for 32 patients with operable N3 neck metastasis undergoing surgical treatment between January 1987 and October 2006. The nuclei of the tumor cells were investigated for the presence of human papillomavirus (HPV) and Epstein-Barr virus (EBV) DNAs and were taken into account as the variable for survival analysis. The primary sites were oropharynx in 11 patients, tongue in 3, buccal mucosa in 1, hypopharynx in 8 and unknown primary in 9. The five-year cumulative overall survival rate was 40.7% and 5-year cumulative regional control rate was 55.8%. The 5-year cumulative overall survival rate of patients with unknown primary site (72.9%) and HPV or EBV positive in the tumor (77.8%) were significantly higher than those patients with known primary site (31.3%) and HPV or EBV negative in the tumor (27.4%), respectively (P = 0.0335 and P = 0.0348, log rank test). In conclusion, surgery with adjuvant therapy offers reasonable outcomes for operable N3 node in head and neck cancer in our cohort. In addition, patients with HPV or EBV positive in the tumor have a better survival.