For polystyrene blends with poly(butyl methacrylate), replacing poly(n-butyl methacrylate) by poly(tert-butyl methacrylate) results in modified topography of spin-cast films (holes dominating at a surface are exchanged with islands, or vice versa, such individual surface features are increased), decreased PBMA surface excess, but similar overall domain structure. Two series (PS/PnBMA and PS/PtBMA) of films with constant thickness and PBMA fraction 0 < Phi < 1, cast from toluene onto silicon wafers, were examined with atomic force microscopy, X-ray photoelectron spectroscopy, profiling and mapping mode of dynamic secondary ion mass spectrometry. Topography was analyzed with the integral geometry approach. Film structure formation was postulated to involve surface segregation, phase separation, and instability of the transient PBMA layer [a linear relation between Phi(2) and averaged size of holes (islands) was observed for PS/PnBMA (PS/PtBMA)]. Structural changes caused by isomer exchange are related to glass transition temperature and blend incompatibility; both increased for PtBMA.