Primary equine mammary tumours are rare entities that are considered to have a poor prognosis (Shank, 2009). In the case report associated with this clinical commentary, the authors describe the clinical presentation, management, and histopathological assessment of a comedocarcinoma arising in the mammary gland of a 20 year-old Arabian mare (Sabiza et al., In press). In their article, the authors allude to some of the challenges of diagnosis and prognostication in cases of equine mammary neoplasia. In spite of a number of detailed descriptions of individual cases or case series of equine mammary tumours, there are numerous unanswered questions regarding carcinomas arising in the equine mammary gland, and the concept of ‘known unknowns’ springs to mind. This clinical commentary will consider a selection of interesting and challenging ‘known unknowns’ relating to the pathogenesis, diagnosis, and prognosis of equine mammary tumours.