The transcription factor, nuclear factor-kappaB (NF-kappaB) is known to play a major role in immune response, inflammation and, via apoptosis and proliferation, also in oncogenesis. Transcription of NFKB1, which encodes the subunit p50/p105 of NF-kappaB, seems to be influenced by an insertion/deletion polymorphism in its promoter region. Accordingly, the goal of this study is to investigate whether this polymorphism can serve as a putative prognostic marker in patients with Squamous Cell Carcinomas of the Head and Neck region (HNSCC). The prognostic value of the -94ins/delATTG NFKB1 promoter polymorphism was analyzed in an unselected series of patients treated with curative intent for HNSCC, including all tumor stages with different therapeutical regimens. Genotyping was performed by means of pyrosequencing, using DNA from paraffin-embedded tissue samples from 364 patients with a median follow-up of 61 (2-143) months. The various genotypes were correlated with relapse-free and overall survival, as well as risk, compared to healthy volunteers. The NFKB1 polymorphism was not related to risk of HNSCC. Kaplan-Meier curves revealed no significant association between the -94ins/delATTG alleles and survival or disease progression of patients with HNSCC. In conclusion, the results suggest that the investigated NFKB1 promoter polymorphism has no prognostic impact on risk or clinical course in HNSCC.