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Considerable clinical and experimental data suggest that vitamin D plays a role in pathogenesis and progression of cancer; nevertheless clinical data for head and neck squamous cell carcinoma (HNSCC) are not available. The aim of our study was to associate tumor and clinical characteristics with status of vitamin D [25-hydroxyvitamin D (25(OH)D)]. 88 patients with newly diagnosed squamous cell carcinoma of the head and neck were included in the study. A blood draw was taken at the time of diagnosis. The observation period lasted from 2006 until 2010. Results: When compared to a cohort from an epidemiological study, serum levels of 25(OH)D were significantly reduced in patients with HNSCC. We furthermore found disease-free survival, as well as overall survival times to be significantly associated with 25(OH)D levels. In conclusion, results from our study suggest an influence of vitamin D status on cancer incidence, as well as on mortality of HNSCC.