Glycosylation is a prevalent and complex type of protein modification central to many biological processes underpinning cancer development and progression. Recent advances in separation science, mass spectrometry and informatics have enabled glycoscientists to study molecular features of the heterogenous cancer glycoproteome including the system-wide mapping of glycosylation sites and glycan compositions to discrete sites. However, significant bottlenecks still exist in determining the glycan fine structures, their site-specific micro- and macro-heterogeneity, their dynamics and cellular origins within in the complex tumour environment. To this end, we have developed an integrated LC-MS/MS-based glycomics, glycoproteomics and proteomics approach that makes use of the Tissue Atlas and Blood Atlas to identify glycoproteome signatures and progression-related changes within the prostate cancer (PCa) and colorectal cancer (CRC) tumour environment. This strategy was first applied to surgically-removed PCa tissues spanning five histological grades (n = 10/grade) and benign prostatic hyperplasia control tissues (n = 5). Grade-specific dynamics of pauci- and oligomannosylation of known bone-marrow and prostate-derived glycoproteins, respectively, and increased N-glycan branching and core 2-type O-glycosylation of known extracellular matrix glycoproteins were found to be key changes associated with PCa progression [1]. In another study, peripheral blood mononuclear cells (PBMNCs) and fresh snap-frozen CRC tissue samples collected from 28 CRC patients spanning four different disease stages (n = 7/stage) and 8 tissue samples from clinically-relevant control individuals were investigated using the same integrated omics strategy. Paucimannosylation was shown to be a significant signature associated with CRC progression in both the tumour tissues and PBMNCs. Correlation analysis between the glycome and proteome datasets showed that the paucimannosidic glycan levels correlated closely with the expression of granulocytic protein markers in the tumour tissues and monocytic protein markers in the PBMNC samples. Collectively, these findings have advanced our knowledge of the molecular and cellular makeup of the PCa and CRC tumour microenvironment by documenting, amongst other key findings, that paucimannosidic glycan-containing proteins of innate immune cell origin are strong yet still largely underexplored signatures of PCa and CRC that may play important roles associated with tumour progression.