Head and neck cancer patients are at high risk for secondary primary cancer (SPC) development. Mutagen hypersensitivity may be associated with elevated risk of SPC. A survey was made of SPC among 124 young (≤50 years) patients with squamous cell carcinoma of the head and neck who were enrolled in a pretreatment mutagen sensitivity investigation during 1996-2006. Mutagen sensitivity was assessed by exposing lymphocytes to bleomycin in vitro and quantitating the bleomycin-induced chromatid breaks per cell (b/c). Patients were classified as hypersensitive (>1 b/c) or not hypersensitive (≤1 b/c). The mean follow-up time was 64 months (range: 5-244 months). Eighteen patients (15%) developed a SPC. The 10-year estimated rate of SPC for hypersensitive (n=65) or not hypersensitive (n=59) patients were 17% and 30%, respectively (p=0.4272). Thirty-nine percent of SPC was developed after 10-year follow-up. The 5-year cancer-specific survival was 17% following the development of SPC. According to our findings, mutagen hypersensitivity does not increase the risk of developing SPC.