Saccharomyces cerevisiae has the most comprehensively characterised protein-protein interaction network, or interactome, of any species. This has been generated through multiple, systematic studies of protein-protein interactions by two-hybrid techniques and through multiple, systematic studies of affinity-purified protein complexes. Despite the quality of this interactome, a question remains as to the extent of interactions that are yet to be detected. These may include interactions that are weak or transient, or those involving proteins that are not amenable to study as two-hybrid fusion proteins. Large scale crosslinking-mass spectrometry (XL-MS) has become possible through the development of cleavable crosslinkers, MS3 methods for peptide analysis and new software. To date, these methods have been applied to analysis of mammalian cells and tissues, to some organelles and to a number of bacterial systems however they have not been applied to yeast. Here we used XL-MS to study intact yeast nuclei, using DSSO, MS3 analysis and XlinkX. Linear peptides identified ~3,300 nuclear-associated proteins, generating the most comprehensive proteome of this yeast organelle to date. A total of ~2,500 crosslinked spectral matches were found, resulting in ~1,350 unique lysine-lysine crosslinks. Of these, 65% were intra-protein crosslinks and 35% were inter-protein crosslinks. Approximately one-third of intralinks mapped to PDB structures, 93% which were less than the <30Å distance constraint. Interestingly, intralinks were found for 437 proteins with no existing structural data. In some cases, such intralinks could refine ab initio structural models. Application of stringent score cutoffs to interlinks yielded a high confidence nuclear interactome. Strikingly, almost half of the interactions were not previously detected by two-hybrid or AP-MS techniques. Multiple lines of evidence existed for many such interactions, whether through replicates, literature or ortholog interaction data. We conclude that XL-MS is a powerful means to measure protein-protein interactions that can complement two-hybrid and AP-MS techniques.