Human sulfotransferase 1A1 (SULT1A1), the most expressed isoform of the phenol SULT1 subfamily, is an important member of sulfotransferase superfamily. A transition, G to A at position 638, in SULT1A1 gene, results in Arg(213)His change. This single nucleotide polymorphism reduces the activity and thermostability of SULT1A1 enzyme. Thus, in the present study the relationship between SULT1A1 Arg(213)His polymorphism and lung cancer was investigated. One hundred and six case and 271 control samples were studied using PCR-RFLP. There was no significant difference in genotype and allele distribution between lung cancer and control populations (p=0.07; p=0.06, respectively). Compared with the SULT1A1*1/SULT1A1*1 genotype the variant SULT1A1 genotype (SULT1A1*1/SULT1A1*2 or SULT1A1*2/SULT1A1*2) was associated with a significantly increased lung cancer risk in cases (p=0.027). In male populations, there was no significant difference between case and controls (p=0.313). In female populations, however, this difference was found to be significant (p=0.04). In smoker and non-smoker populations, no significant relationship was evident between lung cancer and control population (p=0.170, p=0.065, respectively). Statistical analyses of histological types of lung cancer in comparison with the control individuals indicated a significant difference between SULT1A1 Arg(213)His polymorphism and SCC (p=0.027) and other types of cancer, (p = 0.037), except SMCC (p = 0.854). Copyright (C) 2009 John Wiley & Solis. Ltd.