In this work, we are the first to report a detailed comparison between the predictions of a current Computational Fluid Dynamics (CFD) model for describing Fast Pyrolysis Oil (FPO) spray combustion and results from a laboratory-scale experiment. The objectives were to assess the predictive power of the CFD model, evaluate its usefulness in a numerical optimization scenario and characterize the spray flame. The spray flame was produced by using an air-assist atomizer piloted by a CH4/air flat-flame. Pyrolysis oil from a cyclone fast pyrolysis plant was combusted. The flame was characterized by using two-color pyrometry, Tunable Diode Laser Absorption Spectroscopy and high-magnification shadowgraphy. Overall, the assessed model correctly predicted flame structure and seemed appropriate for engineering applications, but lacked predictive power in estimating droplet size distributions. Numerical results were the most sensitive to variations in the initial droplet size distribution; however, seemed robust to changes in the multicomponent fuel formulation. Several conclusions were drawn regarding FPO spray combustion itself; e.g., the amount of produced soot in the flames was very low and droplets exhibited microexplosion behavior in a characteristic size-shape regime.