Despite the rapidly spreading epidemic of tobacco related diseases, little is known of the genetic contribution to current levels of cigarette consumption and nicotine addiction in Egypt. The dopamine D2 receptor gene has been previously suggested to be associated with impulsive/addictive/compulsive behavior. In the present work we investigated the relationship between the dopamine receptor gene DRD2 polymorphism to tobacco behaviors, addiction and subsequent tobacco harm ( as measured by exhaled CO and micronuclei in exfoliated buccal cells) in a cross sectional study of 389 Egyptian male current smokers. These men were recruited from six villages in the Qalyubia governorate in 2004 and their mean age was 40 years +12 (range 19-81). After providing informed consent, study participants were interviewed on their personal characteristics, smoking behaviors, quit attempts, and the Fagerstrom test for nicotine dependence (FTND). Blood samples were obtained from 386 smokers and were genotyped for DRD2. Exfoliated cells of the buccal mucosa were obtained from 265 smokers for micronucleus assay. Exhaled CO was also measured using portable smokerlyzer. The frequency of A1/A1 genotype was 6%, A1/A2 was 29%, and A2/A2 was 65%. The univariate analysis showed no statistically significant association between the A1 allele and the age of onset of smoking, years of smoking, and the average number of cigarettes smoked/day or FTND. However we identified a significant association between the DRD2 genotypes and the maximum duration of time the smokers had been able to quit smoking on their own. No significant association has been found between DRD2 A1 genotype with either exhaled CO or micronuclei in exfoliated buccal cells. These findings suggest that an association between DRD2 genotype and quitting behavior might exist in male cigarette smokers in rural Egypt. Further studies are necessary to confirm this preliminary finding.