Among the cutaneous manifestations, nodular lesions are rather common in Behcet 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 Behcet 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 Behcet syndrome and NV However neutrophil-predominating infiltrate in the subcutis was more common in Behcet syndrome, while necrosis and granuloma formation were encountered more frequently in NV The differences between Behcet 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 Behcet syndrome are mainly neutrophilic vascular reactions with histologic features similar to NV but significantly differing from EN associated with other systemic diseases.