The thermal treatment of Saccharomyces cerevisiae cells, which were homogeneously incorporated into dried wheat flour particles, was performed for various particle radii (0.8 to 1.6, 1.6 to 2.8, 2.8 to 3.2, and 5 mm) and for an initial water activity of 0.20. A new high-temperature short-time process developed by our laboratory for powder decontamination was used at 150, 200, and 250 degrees C for 5 to 30 s, and significant destruction of up to a 6.7-log reduction, depending on treatment conditions and granule size, was achieved. This study confirms the strong influence of granulometry on the microbial destruction of homogeneously contaminated powdered products. Moreover, a thermal model was developed that takes into account the thermal properties of each component, the variations during heat treatment, and the energy required for phase change. This model provides a tool for predicting yeast destruction.