The cellular pathway of follicle-stimulating hormone (FSH) and its receptor (FSHR) is typically involved in reproduction in mammals. In humans, the FSHR is normally found in cells of the testis and the ovary, while it is scarcely expressed in other normal tissues. The expression of FSH/FSHR is studied in prostate, thyroid, and ovarian cancer tissues. Recently, the expression of FSHR was uniformly documented in malignant vascular endothelial cells from different tumor types, while in normal or inflammatory tissues its expression was scarce, suggesting a potential role of a pan-receptor in cancer. Subsequent studies have attempted to verify this unique specificity of this molecule and further define its features in malignant microenvironments but have had conflicting results, mostly because of differing techniques and immaturity of antibodies. Still, the lack of FSHR expression in most non-cancerous cells, in contrast to its specific correlation with the malignant tissue microenvironment, implies a potential role as both a diagnostic and a therapeutic tool. FSHR might also have a very specific role in malignancies, such as angiogenic and/or growth factor malignancies, but this is yet to be validated. Moreover, the expression of FSHR in endothelial malignant cells could have a predictive impact on disease progression, especially in relation to therapies targeting the tumor vasculature. In this review we look deep into the physiology of the FSH/FSHR pathway and evaluate the potential of FSHR as a predictive and prognostic tool in oncology.