Xanthomas of the skin are dramatic lesions and have long been noted and studied by physicians. Until the last quarter century, however, little differentiation of the various types and the accompanying systemic defects was made. Since then, various investigators have clarified the problem, but at the same time have led into perplexing fields of lipid metabolism, reticulo-endothelial disease and genetics (1, 2). The prime differentiation is made on clinical, pathological and chemical evidence separating the diseases of the reticulo-endothelial system from the group of where an error in lipid metabolism is most likely primary. In Table I is given the working classification used in this study. The first group, primary reticulo-endothelial disease with xanthomas, includes Letterer-Siwe disease, Hand-SchUller-Christian disease, cosinephilic granuloma of bone, xanthoma disseminata, and nevoxantho-endothelioma. Evidence is accumulating that the above syndromes are but variations of the same disease process. The second group, the lipidoses associated with xanthoma, exhibits some defect in fat metabolism which is reflected in the lipids of the serum. This group is best separated into primary and secondary forms. The primary form, or primary familial lipidoses, shows of plane and tuberous type, characteristically on the knees, buttocks, elbows, palms, soles and digits. Other external manifestations are tendon sheath xanthoma. Frequently, or perhaps inevitably, severe cardiovascular disease will be associated. Any of the above manifestations may exist simultaneously or separately, and extensive genetic studies indicate that this syndrome is merely the extreme manifestation of a much more wide-spread inherited defect. The secondary lipidoses includes of plane, tuberous or eruptive type, occasionally seen in various types of liver disease, diabetes, chronic pancreatitis and myxedema. The inclusion of the syndrome of idiopathic hyperlipemia with hepato-splenomegaly in this group may be faulty, but suffices for the present study. A third large group is made up of miscellaneous conditions showing foam cells in cutaneous lesions but are not true xanthomas and are not listed in the table.