Fatty acid (FA) homeostasis is a process tightly regulated by synthesis and degradation. Acetyl coenzyme A carboxylase (ACC) 1 and ACC2 are the rate-limiting enzymes involved in catalysing the carboxylation of acetyl-CoA to malonyl-CoA for synthesis and degradation, respectively. The reprogramming of energy metabolism is one of the hallmarks of cancer, and can be achieved by exploitation of this pathway. Mammary epithelial cells do not normally express ACC1, but following the initiation of carcinogenesis, even in a premalignant stage, the upregulation of this protein is evident. It is thought that the subsequently generated FAs can be involved in various aspects of tumorigenesis such as increasing substrates for beta-oxidation, enhanced proliferation, protecting malignant cells from therapeutics, creating lipid rafts for cell signalling and aiding metastatic dissemination. This study demonstrates a significant role for ACC1 in vivo, with ACC1 knockout mice resulting in delayed mammary tumour formation and decreased incidence of metastasis. In vitro ACC1 siRNA administration further demonstrates ACC1 function in breast cancer cell migration. In addition, to my knowledge, this is the first study to investigate the presence and role of ACC2 in breast cancer in vivo and in vitro. This was determined through the use of immunohistochemistry and real-time PCR. In vitro administration of ACC2 siRNA indicates a potential role for this protein in breast cancer cell proliferation, migration and invasion. Furthermore, combined knockdown of ACC1 and ACC2 siRNA had an additive effect on the inhibition of cancer cell migration and invasion compared to ACC1 alone. These data indicate several novel functions for ACC1 and ACC2 during breast cancer progression.