Breast carcinogenesis is a multistep and multipath disease process which occurs in the epithelium lining of the ductal system in the vast majority of cases. Several studies have shown that the relative risk of breast cancer is increased in every step of this progression and many tumour associated antigens or biomarkers appear during each phase of carcinogenesis. However, their ability to predict for a substantial likelihood of developing breast cancer remains unclear. The acquisition of breast tissue samples, representative of an individual's cellular stability and subcellular biochemical and molecular state could lead to definition of surrogates for risk, early detection, pharmacodynamic determination and finally chemopreventive intervention. The intraductal approach includes nipple aspiration fluid (NAF), ductal lavage (DL) and mammary ductoscopy (MD). These techniques together with random periareolar fine needle aspiration (RPFNA) represent the available techniques for the sampling of breast fluid and exfoliated epithelial cells. At the moment, these procedures are not considered a screening procedure for early breast cancer detection but might provide a powerful research tool for studying breast carcinogenesis in vivo. We summarize the current knowledge regarding the vast array of molecules involved at all stages of carcinogenesis, which can be studied by intraductal approach, and the possibility to utilize them as candidate biomarkers to refine risk assessment, and their possible use in prevention strategies.