Inflammatory breast cancer (IBC) is a rare and aggressive disease that accounts for ~2-4% of all breast cancers. However, despite its low incidence rate, IBC is responsible for 7-10% of breast cancer-related mortality in Western countries. Thus, the discovery of robust biological targets and the development of more effective therapeutics in IBC are crucial. Despite major international efforts to understand IBC biology, genomic studies have not led to the discovery of distinct biological mechanisms in IBC that can be translated into novel therapeutic strategies. In this Review, we discuss these molecular profiling efforts and highlight other important aspects of IBC biology. We present the intrinsic characteristics of IBC, including stemness, metastatic potential and hormone receptor positivity; the extrinsic features of the IBC tumour microenvironment (TME), including various constituent cell types; and lastly, the communication between these intrinsic and extrinsic components. We summarize the latest perspectives on the key biological features of IBC, with particular emphasis on the TME as an important contributor to the aggressive nature of IBC. On the basis of the current understanding of IBC, we hope to develop the next generation of translational studies, which will lead to much-needed survival improvements in patients with this deadly disease.