The present study was undertaken to examineCYP1A1andXRCC1polymorphisms as potential genetic susceptibility markers for laryngeal squamous cell carcinoma (SCC). Eighty-eight patients with laryngeal SCC and 178 randomly selected healthy blood donors from the same Caucasian population (Porto, Northern Portugal) were analysed forCYP1A1(MspIandNcoI) andXRCC1(Arg194Trp and Arg399Gln) polymorphisms, using PCR-RFLP techniques.CYP1A1 MspIMH (mutant homozygous) andCYP1A1 NcoIHT (heterozygous) genotypes were more frequent in patients than in controls, with those carrying aCYP1A1 NcoIHT genotype having a 2.3-fold higher risk for tumour development. On the other hand, polymorphisms inXRCC1codon 399 and codon 194 do not seem to play a role in the aetiology of smoking-related laryngeal SCC, once its distribution was similar in both analysed groups. All the significant associations observed were exclusively due to differences between controls and larynx glottic cancer patient subgroup. Furthermore, lower lifetime tobacco consumption was observed in laryngeal SCC patients carrying theMspIandNcoIpolymorphisms, than in those who did not show the polymorphic variants. This investigation seems to support the importance ofCYP1A1gene polymorphism as a potential genetic marker of laryngeal cancer development, specially concerning smokers who have inherited the at-risk genotypesCYP1A1 MspIMH orCYP1A1 NcoIHT, who do appear to be more susceptible to the development of SCC of the glottic larynx.