Mesenteric panniculitis is an extremely rare inflammatory condition of the adipose tissue of unknown etiology. It is characterized by extensive, progressive fibrosis of the mesenteric fat tissue, leading to tumor formation. Clinical manifestations vary according to the process involving the structures. Abdominal pain accompanied by nausea, malaise, pyrexia, and weight loss and a poorly defined mass are common presentations. Major pathologic changes include (1) degeneration of mesenteric fat, (2) an inflammatory reaction, and (3) fibrosis of the adipose tissue. We present four patients with an aggressive form of mesenteric pannicultis with characteristic histopathologic features. We discuss the relationship between the histopathologic features and the surgical intervention in these cases.