Two methodologies to propagate the uncertainties on the nuclide inventory in combined Monte Carlo-spectrum and burn-up calculations are presented, based on sensitivity/uncertainty and random sampling techniques (uncertainty Monte Carlo method). Both enable the assessment of the impact of uncertainties in the nuclear data as well as uncertainties due to the statistical nature of the Monte Carlo neutron transport calculation. The methodologies are implemented in our MCNP–ACAB system, which combines the neutron transport code MCNP-4C and the inventory code ACAB. A high burn-up benchmark problem is used to test the MCNP–ACAB performance in inventory predictions, with no uncertainties. A good agreement is found with the results of other participants. This benchmark problem is also used to assess the impact of nuclear data uncertainties and statistical flux errors in high burn-up applications. A detailed calculation is performed to evaluate the effect of cross-section uncertainties in the inventory prediction, taking into account the temporal evolution of the neutron flux level and spectrum. Very large uncertainties are found at the unusually high burn-up of this exercise (800 MWd/kgHM). To compare the impact of the statistical errors in the calculated flux with respect to the cross uncertainties, a simplified problem is considered, taking a constant neutron flux level and spectrum. It is shown that, provided that the flux statistical deviations in the Monte Carlo transport calculation do not exceed a given value, the effect of the flux errors in the calculated isotopic inventory are negligible (even at very high burn-up) compared to the effect of the large cross-section uncertainties available at present in the data files.