Adipose is a metabolically active and complex tissue consisting of macrophages, lymphocytes, endothelium, mesenchymal stem cells, and mature adipocytes. There are significant structural and functional differences between adipose derived from lean and obese humans. Adipose from obese humans with metabolic syndrome secretes a very different milieu of active cytokines, compared to healthy adipose. Culturing mature intact adipose tissue derived from adipose biopsies or surgically resected organs presents new opportunities to study the complex signals between adipose and epithelia. Normal human adipose adapts well in contemporary 3-dimensional culture technologies. The micrograph shown on the cover (40× magnification) shows intact mammary adipose stained for actin (red) and neutral fatty acids with BODIPY^493/503 (green) to identify adipocytes. Conditioned media collected from adipose in culture enables analysis of the secretome and further exploration of both paracrine and endocrine effects of adipose-derived cytokines on vulnerable epithelial targets. The publication of Esper et al. (p. 1174) in this issue of Cancer Prevention Research reports that leptin secretion from human adipose correlates with expansion of normal human mammary stem cell spheres. Adipose-derived adiponectin is inversely correlated with normal human mammary stem cell sphere formation. This model provides a useful platform for studies aimed at dissecting the relationship between the obesity-associated metabolic syndrome and carcinogenesis.