Since studies in vitro have shown effects of IGFBP-3 on both fat cell differentiation and mammary tumor cell growth, this in vivo study aimed to determine the influence of IGFBP-3 on the development of obesity in response to high-fat feeding and on the subsequent growth of syngeneic mammary tumors in an immune-competent mouse model. Here, IGFBP3 is linked to obesity due to melanocortin 4 receptor deficiency.