The pathogenetic mechanism of nasopharyngeal carcinoma (NPC) is still unclear. Its familial aggregation, on the other hand, has been well documented by many epidemiological studies. The objective of this study was to evaluate the clinical characteristics of familial NPC in an endemic region. Between March 1994 and November 2005, 1,202 consecutive patients were treated at our institution. Patients were divided into 2 groups according to their family history: group 1 had at least one first-degree relative with NPC at the time of diagnosis, and group 2 did not. There were 125(10.4%) patients in group 1, 66% of them had diseased siblings, 44% had diseased parents and 2% had diseased offspring. The patients in group 1 were on average about 2 years younger than group 2 at diagnosis (47.9 vs. 49.8, P = 0.04). There were also more stage I-II patients in group 1 (38 [corrected] vs. 23%, P < 0.01). Although the 5 year overall survival was also higher with group 1 (79 vs. 69%, P < 0.01), only age, sex, T classification and N classification were found to be significant independent factors but not family history per se (P = 0.10). Similar findings were observed after excluding screen-detected patients from group 1. The high incidence of familial clustering and improved outcomes from early detection highlight the importance of screening among these high risk family members.