Background: Diffuse plane xanthoma (DPX) usually has been described in association with a reticuloendothelial disease. However, the incidence of an underlying disease and its relation to clinical and histopathologic features have not been previously described. Objective: We describe the clinicopathologic features of a series of patients with DPX. Methods: Eight patients with DPX were diagnosed and studied between 1987 and 1996. Results: Three of the 8 patients had a reticuloendothelial disease (benign monoclonal gammopathy in 2 and chronic myelomonocytic leukemia in 1). These 3 patients had larger cutaneous lesions and involvement of trunk and extremities. Histologic examination showed only foamy macrophages in 2 of the 8 patients. The remainder exhibited macrophages, foamy histiocytes, lymphocytes, and Touton cells. Conclusion: The incidence of underlying disease associated with DPX seems to be lower than expected. However, patients with DPX should be observed for the potential occurrence of an associated condition. (J Am Acad Dermatol 1998;39:439-42.)