Pyrochemical processing (pyroprocessing) was developed to recover plutonium that is inherently comingled with minor actinides, uranium, and fission products and has been studied with the aim of recovering actinide elements from spent nuclear fuel. Although a significant amount of attention has been given to pyroprocessing technology as a future fuel recycling system, safeguards approaches are challengeable because of a lack of international experience with safeguarding pyroprocessing facilities beyond those at a pilot scale. Safeguards have primarily depended on nuclear material accountancy with the measurement uncertainties inherent in nuclear material flow. When the weakness of nuclear material accountancy is addressed, the quantity of material unaccounted for (MUF) is generally regarded as an important measure of the safeguardability of a facility. Statistically, the observed MUF is a random variable that is an estimate of the true MUF because the observed MUF is affected by measurement errors. The MUF uncertainty can be calculated by properly combining the random error and systematic error of the nuclear material accounting measurement. Therefore, in this study, a conceptual design for estimation of the uncertainty of MUF that can occur in a reference pyroprocessing facility (REPF) is developed, where REPF is a model used to optimize the safeguardability of a future pyroprocessing facility.