Among the cutaneous manifestations, nodular lesions are rather common in Behçet syndrome. The histologic nature of these lesions has been a matter of controversy. To establish their distinguishing features, biopsy specimens from nodular lesions of 24 patients with Behçet syndrome, 25 with nodular vasculitis (NV), and 20 with erythema nodosum (EN) were compared. Statistical analysis revealed insignificant differences between most of the histologic features of Behçed syndrome and NV. However, neutrophil-predominating infiltrate in the subcutis was more common in Behçet syndrome, while necrosis and granuloma formation were encountered more frequently in NV. The differences between Behçed syndrome and EN were more significant. Septal panniculitis, lymphocyte-predominating infiltrate, absence of many vascular changes as well as vasculitis, and necrosis were features in favor of EN. Nodular lesions of Behçet syndrome are mainly neutrophilic vascular reactions with histologic features similar to NV but significantly differing from EN associated with other systemic diseases.