The extracellular matrix (ECM) prevents invasion of tumour cells and possesses an intrinsic mechanism to down-regulate signalling processes that promote cancer proliferation. Small Leucine Rich Proteoglycans (SLRPs) are ubiquitous ECM components involved in matrix structural organization and as such can potentially regulate cancer cell multiplication, angiogenesis and migration. Decorin, a class I SLRP that modulates collagen fibrillogenesis, also functions as a natural pan-tyrosine kinase inhibitor to reduce tumour growth. In fact, decreased decorin expression has been associated with tumour aggressiveness and lower survival. In contrast, biglycan, another class I SLRP, was highly expressed in cancer and was associated with metastatic activity and lower survival. Tissue expression of lumican, a class II SLRP, was associated with clinical outcome and appears tumour specific. Recently, decorin, biglycan and lumican were found to be potential biomarkers in bladder cancer. This review updates our current understanding on the molecular interplay and significance of decorin, biglycan and lumican expression in cancer.