Using physiologically-based pharmacokinetic (PBPK) modeling, occupational, personal, and environmental benzene exposure scenarios are simulated for adult men and women. This research identifies differences in internal exposure due to physiological and biochemical gender differences. Physiological and chemical-specific model parameters were obtained from other studies reported in the literature and medical texts for the subjects of interest. Women were found to have a higher blood/air partition coefficient and maximum velocity of metabolism for benzene than men (the two most sensitive parameters affecting gender-specific differences). Additionally, women generally have a higher body fat percentage than men. These factors influence the internal exposure incurred by the subjects and should be considered when conducting a risk assessment. Results demonstrated that physicochemical gender differences result in women metabolizing 23–26% more benzene than men when subject to the same exposure scenario even though benzene blood concentration levels are generally higher in men. These results suggest that women may be at significantly higher risk for certain effects of benzene exposure. Thus, exposure standards based on data from male subjects may not be protective for the female population.