Diffuse and symptomatic lipomatosis of the colon, particularly when associated with hyperplasia of the appendices epiploicae, is a rare disease. We report here the case of a lean, 26-year-old woman who had polypoid lipomatosis of the colon with submucosal and subserous expression (involving the mesentery and peritoneum) associated with extreme hyperplasia of the appendices epiploicae. Her disease led to a recurrent subocclusive syndrome which required total colectomy. We discuss the case and review the literature on this subject. The particular characteristics of this case and early onset of disease would suggest that our patient was affected by a congenital lipomatous syndrome linked to mesenchymal dysplasia. Long-term monitoring will enable prompt intervention in the case of reformation of lipomatous tissue.