Nasopharyngeal carcinoma (NPC) is rare in most of the world but common among southeast Asians. Since NPC is usually diagnosed at relatively young ages and most patients now survive, the issue of second primary tumors (SPTs) has become important. Previous studies of SPTs among NPC survivors have given conflicting results. Data on patients with NPC diagnosed between 1996 and 2002 were abstracted from the medical records of two Hong Kong oncology centers. SPT incidence in these patients was compared to that of Hong Kong's general population using standardized incidence ratios (SIR). Eight-four patients were observed to have at least 1 SPT and 92 total additional cancers (SIR = 1.93, 95% CI = 1.55-2.37). The excess risk was greater for women and patients under 40 at diagnosis. Significant excesses were found for tongue, lung, nasal and middle ear, and brain cancers. The pattern of sites at which the greatest excess risk occurred is consistent with the hypothesis that much of the excess is due to treatment effects. The greater excess risk among patients diagnosed before 40 points to possible genetic influences. More research is needed to determine the reasons for greater excess risk among women.