Le NS, et al. - In patients with cancer of unknown primary (CUP) of the head and neck, researchers analyzed and compared ipsilateral and bilateral adjuvant radiotherapy. Overall survival, recurrence-free survival and radiation-induced side effects were evaluated in 76 CUP patients who received either ipsilateral (n = 29) or bilateral (n = 47) radiotherapy. The 5-year overall survival and recurrence-free rate were 67.9% and 71.5%, respectively, at a median follow-up of 41 months. There was no statistically significant difference in overall 5-year survival, recurrence-free survival, occurrence of a primary tumor, and distant metastasis between ipsilateral and bilateral radiotherapy. Analysis of acute side effects caused by radiation showed a significant advantage of ipsilateral radiotherapy. Since the study's main parameters of outcome and radiation-induced side effects showed no benefits of bilateral radiotherapy, the ipsilateral radiotherapy strategy for adjuvant treatment of CUP patients may be recommended.