A mathematical model for the anode of a direct methanol fuel cell (DMFC) is presented. This model considers the mass transport in the whole anode compartment and the proton exchange membrane (PEM), together with the kinetic and ohmic resistance effects through the catalyst layer. The influence of key parameters on methanol crossover and anode performance is investigated. Our results indicate that, at low current density and high methanol concentration, the methanol crossover poses a serious problem for a DMFC. The anodic overpotential and reaction-rate distributions throughout the catalyst layer are more sensitive to the protonic conductivity than to the diffusion coefficient of methanol. Increasing the protonic conductivity can effectively enhance the performance of a DMFC.