The effect of DUPIC fuel composition heterogeneity on CANDU core performance was assessed for three candidate DUPIC fuel options: the fissile content adjustment method, reactivity control by slightly enriched and depleted uranium, and reactivity control by natural uranium. The fissile content adjustment method produces DUPIC fuel of fixed 235U and 239Pu contents, while the reactivity control method produces DUPIC fuel of uniform reactivity at the fresh condition. To assess the uncertainty of the core performance parameter associated with the isotopic variation, the sensitivity coefficients were generated by the generalized perturbation theory for the lattice parameter and zone controller level perturbations. The uncertainty was then estimated for three key core performance parameters: maximum channel power (MCP), maximum bundle power (MBP), and channel power peaking factor (CPPF). The fissile content adjustment method was shown to have a smaller uncertainty in the core performance parameter than with the reactivity control options. For the fissile content adjustment method, the average uncertainties of MCP, MBP, and CPPF were estimated to be 1.3, 2.5, and 1.2%, respectively, with 95% confidence level, when simulated for specified burnup points of the equilibrium core.