The recent improvements in proteomics technologies have enabled the distribution and relative abundances of proteins to be characterized across tissues in unprecedented detail. These studies have shown that even tissues from unrelated developmental lineages are composed of extremely similar protein repertoires, suggesting that additional layers of co-ordination are responsible for tissue functionality. As the ability of proteins to form higher order associations, also known as protein complexes, allows for dramatic changes in functionality by the exchange of subunits global differences within tissues interactomes may account for tissue functionality. As traditional high-throughput protein-protein interaction (PPI) approaches are untenable for tissues, we have applied an alterative means to explore this hypothesis by use of size exclusion chromatography protein correlation profiling SILAC (SEC-PCP-SILAC). Using a super-SILAC based approach, we profiled the interactome landscape of seven tissues (Brain, Lung, Liver, Heart, Skeletal Muscle, Thymus and Kidney), and we generated quantitative profiles of protein distributions across both SEC fractions and between tissues. Protein chromatograms across the SEC gradients were assessed based on correlation and co-enrichment, to determine PPIs using the principle of guilt by association. Using our PCP-SILAC approach, 7054 protein groups were identified across the seven tissues, with 5231 enabling the mapping of protein profiles. From these profiles, 36554 protein interactions could be determined with a precision of ~68% based on comparison to the CORUM database., Over 80% of proteins were observed in all tissues, indicating that at the protein level these tissues were extremely similar, however of note only ~30% of interactions were shared between tissues. Between functionally related tissues, this overlap increased to >60% consistent with the interactome shaping function. In total, 3304 protein complexes were mapped across tissues with the majority showing high similarity in membership (>0.75), however tissue specific exchanges of subunits were common. Taken together, we observed that complex heterogeneity between tissues is extremely common, and may shapes the functionality of tissues.