Tumour-promoting stromal changes is an early event in breast cancer. They have been proposed as therapeutic and diagnostic targets but with minimal translational success. This project aims at evaluating “cystine rich with EGF like domains 2” (CRELD2) – a tumour cells’ secreted protein that mediates breast cancer-tumour-stroma crosstalk, as the first in class biomarker of the early invasive breast cancer. This is a prospective, correlational study. 58 breast cancer patients were recruited from the RAH Breast Department. Intra-operative tumour core biopsy tissues used to assess CRELD2 levels. This data was analysed against the patient’s tumour and disease phenotypes. Ten patients with high levels of detectable CRELD2 and 10 patients with low/no CRELD2 were used for further stromal assessment. This subset of patients’ tumour slides was stained for stromal components associated with cancer-associated fibroblasts. The fluorescence signal was measured using intensity density in the average of 10 region of interest sections per patient. Results: This pilot study had shown that the presence of intra-tumoural CRELD2 levels was strongly correlated with known prognostic characteristics such as: T stage, lymph node metastasis (p value <0.05) and tumour grade (p=0.07). All stromal characteristics tested were increased in patients with high intra-tumoral CRELD2 levels compared to patients who had no/low CRELD2 levels. Conclusion: Our findings show the utility of CRELD2 as a novel biomarker of early invasion of breast cancer. Despite the many prognostic factors known at the diagnostic stage size of tumour and grade of tumour, these still do not accurately predict for lymph node metastasis. This pilot study has shown CRELD2 as an independent predictive marker of local metastasis to lymph nodes. Alterations in breast cancer stroma is also shown in this cohort and supports the functional action and pro-tumorigenic property of CRELD2 that should be considered for future targeted therapy in breast cancer.