This research addresses the erosive resistance of a hypereutectic high-chromium cast iron subjected to solid particle erosion. The study stems from a specific application of high-chromium cast iron, i.e., the critical surfaces of large industrial fans operating in a cement clinker grinding plant where such damage is a limiting factor for the components’ lifespan. A dedicated experimental investigation on the impact of substrate microstructure and erodent particle size on erosion resistance was set. The experimental campaign, conducted on a dedicated test bench per the ASTM G76 standard, comprised the analysis of the as-received, tempered, and destabilized conditions for the cast iron. From a preliminary image analysis of the microstructural features, two diameters of the erodent powder for the erosion tests were defined. The observed erosion rate decreased with the increase in the mean particle diameter of the erodent, indicating more severe erosive conditions for smaller particles. From the analysis of the worn surfaces, it was possible to highlight the involved mechanisms concerning the considered test combinations. For the as-received condition, the erosion rate with the larger mean particle diameter of the erodent decreased three times compared to the smaller one. For the heat-treated conditions, the erosion rate was halved with the larger mean particle diameter of the erodent. The proposed analysis, intended to acquire more insight into the limiting factor for the components’ lifespan for erosive wear damage, proved that erosion resistance is not dependent on the material’s hardness. The contribution of the mean particle diameter of the erodent is predominant compared to the substrate conditions.