In spite of this study’s limitations and the need for prospective studies with larger sample sizes, the findings suggest that the presence of GSTM1 and GSTT1 null polymorphisms and CYP1A1 3 rs4646903 T>C are associated with a higher risk of developing larynx cancer in male Caucasian smokers in southeastern Spain. Here, CYP1A1 is linked to laryngeal neoplasm.