A recent study in prostate cancer has revealed that infiltration by nerve fibres is essential for tumour progression and can be targeted for future therapeutic strategies (Magnon et al. 2013, Science 341:1236361). In breast cancer, the current dogma is that primary cancers are rarely infiltrated by nerve fibres, however supporting evidence is sparse and predates the use of neuronal markers. In this study, the presence of nerve fibres in primary breast cancers was investigated by immunohistochemistry with the neuronal markers PGP9.5 (all types of nerve fibres) and tyrosine hydroxylase (sympathetic fibres) in a series of 319 clinically annotated breast tumours. Isolated nerve fibres were observed in 20% of breast cancers. There was an association with histological subtypes: 28% of invasive ductal carcinomas contained nerve fibres as compared to only 12% of invasive lobular carcinomas (p=0.001). In addition a correlation was found between nerve fibres and the expression of nerve growth factor (NGF) in cancer cells (p=0.0001), suggesting that the secretion of NGF by cancer cells induces axonogenesis in breast tumours. This was confirmed in vitro, as breast cancer cells stimulated axonogenesis in neuronal cells that was inhibited by blocking anti-NGF antibodies. Interestingly, the presence of nerve fibres in breast tumours was associated with lymph node invasion (p=0.0031), indicating a relationship with metastatic potential and poor prognosis. Furthermore, primary neurons were able to stimulate the invasion of breast cancer cells in a Transwell assay, suggesting that nerve fibres participate in breast cancer progression. In conclusion, infiltration by nerve fibres is an underestimated feature of some breast cancers that appears to be driven by NGF and is related to tumour aggressiveness. The potential clinical implication of using nerve fibres detection and targeting for innovative prognosis and therapeutic strategies in breast cancer should be further explored.