The distribution of mass density through the thickness of Medium Density Fiberboard (MDF) panels is known to be non-uniform. A few studies have previously investigated the influence of this non-uniform through-thickness density distribution on the thermal behavior of MDF panels in small-scale tests. This study assesses the significance of this material property on flame spread simulations in a medium-scale set-up, namely that of Single Burning Item (SBI) corner fire tests. Simulations are performed using FireFOAM 2.2.x, considering both uniform and non-uniform MDF material density profiles, using model-effective material properties determined from bench-scale pyrolysis tests conducted in a Fire Propagation Apparatus (FPA). The heat transfer from the gas phase is modeled by means of empirical expressions with adjusted parameters. The simulations are assessed against the results of several SBI experiments with MDF panels and a test with Calcium Silicate (CS) panels. When the non-uniform nature of the through-thickness density is taken into account, the fire growth prediction in terms of the total Heat Release Rate (HRR) is considerably different (20% higher peak HRR), mainly due to the characteristic high peak mass loss rate at the initiation of pyrolysis of MDF material, resulting from the higher mass density near the surface of the panels. Furthermore, total heat fluxes on the panels, lateral flame spread, surface pyrolysis and through-thickness char formation visibly depend on the non-uniform distribution of mass density, particularly in regions further away from the corner where the influence of thermal attack from the burner is less dominant. A new diagnostic is proposed for determining the pyrolysis front location and spread on the surface of the charring panels.