In recent years, rapidly accumulating evidence implicates forkhead box C1 () in cancer, especially in studies of basal-like breast cancer (BLBC). Other studies have followed suit, demonstrating that is not only a major player in this breast cancer subtype, but also in hepatocellular carcinoma (HCC), endometrial cancer, Hodgkin's lymphoma (HL), and non-Hodgkin's lymphoma (NHL). The gene encodes a transcription factor that is crucial to mesodermal, neural crest, and ocular development, and mutations found in have been found to cause dominantly inherited Axenfeld-Rieger Syndrome (ARS). Interestingly, while missense mutations that are associated with ARS usually reduce gene activity, increased function now appears to be often linked to more aggressive cancer phenotypes in BLBC, HCC, HL, and NHL. This review discusses not only the role of in cancer cell progression, proliferation, differentiation, and metastasis, but also the underlying mechanisms of how can contribute to aggressive cancer phenotypes.