Breast spindle cell lesions (BCSLs) are a highly heterogenous group of diseases that frequently challenge the diagnostic skills of even specialist breast pathologists. While a systematic morphological assessment remains central to narrowing the differential diagnosis, immunohistochemistry (IHC) is a valuable ancillary test that can help to either further narrow or confirm a diagnosis. However, BSCLs can also show a remarkable degree of intra-tumoural morphological and immunohistochemical heterogeneity, meaning that IHC is rarely either specific or sensitive for a particular lesion and that care must be taken when interpreting diagnostic core biopsies. IHC results must, therefore, always be interpreted with caution and in the context of the morphological features and wider clinicopathological findings.