GDF-15 (Growth Differentiation Factor-15) is a member of the transforming growth factor β (TGF-β) superfamily. GDF-15 is not only involved in cancer development, progression, angiogenesis and metastasis, but also controls stress responses, bone formation, hematopoietic development, adipose tissue function and cardiovascular diseases. GDF-15, which is regulated by p53, has shown antitumorigenic and proapoptotic activities in vivo and in vitro. Also, GDF-15 is involved in skin biology and histamine-induced melanogenesis; it is overexpressed in melanoma cells and is associated with depth of tumor invasion and metastasis. GDF-15 level is increased in patients with systemic sclerosis and is related with the degree of skin sclerosis and intensity of pulmonary fibrosis. In the future, GDF-15 may be a potential target for therapy in benign disorders with skin fibrosis and malignant lesions of the skin.