The instability, dynamics, and dewetting engendered by the van der Waals forces in a thin liquid film sandwiched between a solid substrate and bulk fluid phase are investigated based on linear stability analysis and large-area, nonlinear 2D and 3D simulations. The effects of initial free-surface heterogeneities on the length scale of instability, morphology, order of the resulting structures, and their dynamic evolution are examined. The simulations clearly show two distinct regimes of spinodal instability: (a) deep inside the spinodal territory (DIST) and (b) a defect-sensitive spinodal regime (DSSR). The latter regime with increased sensitivity to the initial conditions and local ordering and clustering of holes is obtained toward the periphery of the spinodal region where spinodal destabilization becomes weak, or the force per unit volume ∂φ/∂h f 0. Thus, relatively thin and thick films close to the spinodal boundaries that do rupture by the spinodal mechanism may give the appearance of nucleation-induced rupture. Finally, the effects of simulation domain size (or number of holes) on the morphological and dynamic characteristics of spinodal instability are studied to assess the minimal sample size of simulations required to faithfully mirror some important aspects of thin-film rupture.