Comparative proteomic analyses in ecotoxicology and related fields require reproducible display of as many proteins as possible. In addition, it should be possible to carry out a quantitative comparison in a reliable manner. Sample preparation represents one of the essential steps toward these aims. In their work, Wu et al. describe how to deal with different recalcitrant tissues of varying species (Proteomics 2013, 13, 3205–3210). Their work underlines the necessity to adapt sample preparation to the specific requirements of the biological material. Beyond that Wu et al. present TRIzol® as feasible means for combined extraction of proteins and RNA. Indeed, using TRI-reagent extraction for proteomics, they resolve two problems at a time: that of removing contaminating compounds and that of simultaneous analysis of gene and protein expression.