This paper presents the use of the quartz microbalance with dissipation combined with surface plasmon resonance to probe protein adsorption at nanopatterned surfaces. Three different types of adsorbing materials, representing rigid discrete nanoparticles, dense protein films and soft low density films have been studied on systematic varied circular nanostructures in the 100 nm to 1000 nm size range. Analysis and quantification of the QCM-D response from larger nanostructures could be understood and quantified in the same way as for homogeneous surfaces, while that for nanostructures of 100 nm and 200 nm diameter was significantly underestimated. Our findings suggest a size limitation of those techniques in analysis of adsorption at nanofeatures.