Risk factors for distant metastases are a matter of debate. This aspect has been recently exhaustively reviewed by Leon et al9 and is beyond the scope of the present study. Overall, our results confirmed that the locoregional control and N stage are markedly associated with an increased probability of developing distant metastases. There is a general consensus on these specific risk factors.6,8- 11,13,18- 20,25- 28 Furthermore, our results highlight some other factors that may play a role. Indeed, cancer localization, histologic grade, local extension of tumor (T stage), and, to a lesser extent, younger age were significantly associated with the risk of distant metastases. Results from the present study suggest that the hypopharynx is the site at highest risk of subsequent distant metastases. Specifically, this localization was associated with a relative risk of 13.7 (95% CI, 7.1-25.4) when compared with cancer of the oral cavity, which conversely resulted in identifying those at lowest risk. There are reports9- 11,27 that some localizations in the head and neck, such as in the nasopharynx and hypopharynx, had a greater risk. Leon et al9 found that cancers of hypopharynx and supraglottis were independent risk factors for distant metastases. Conversely, according to other authors,8,13,20,22,28 the site of the tumor had no significant influence on the development of distant metastases. Furthermore, there is disagreement as to the influence of the histologic grade and local extension of the tumor in the appearance of distant metastases.6- 10,12,13,20,27,28 However, results from one of the largest series on this topic univocally support a significant association between the risk of distant metastases and the local extension.9 In our study, we documented a relationship between local extension and risk of distant metastases. Finally, to our knowledge, an increased risk in patients younger than 45 years has not been previously reported.29,30 In this regard, though, it should be noted that the entity of this risk is less relevant when compared with other factors such as localization, local extension of tumor, and N stage. Overall, it may be speculated that the role of younger age is presumably of limited importance. Discrepancies among studies are difficult to explain. It might be hypothesized that the reduced sample size and thus the low power of many currently available studies may in part explain these conflicting results. Differences in the epidemiological profile of patients among studies may also play a role.