Lysosomal-associated membrane protein-2 (LAMP-2) is a target antigen for anti-neutrophil cytoplasmic antibodies (ANCAs), which are closely linked to a subset of primary systemic vasculitides. Cutaneous polyarteritis nodosa (CPN) is a necrotizing vasculitis of small to medium-sized arteries within the skin. We measured levels of serum anti-LAMP-2 antibody in 50 patients with CPN, 8 with microscopic polyangiitis (MPA), and 34 healthy persons. We also investigated the presence of ANCA in patients with CPN using indirect immunofluorescence (IIF), a direct ELISA and a capture ELISA specific for myeloperoxidase (MPO) and proteinase 3 (PR3). Serum anti-LAMP-2 antibody levels differed significantly between patients with CPN (0.263 U/ml) and those with MPA (0.180 U/ml) (p = 0.0102). Serum of all patients with CPN was negative for MPO-ANCA and PR3-ANCA by both direct ELISA and capture ELISA. In contrast, IIF assay revealed ANCA in 42 (84.0%) of the 50 CPN patients. Serum anti-LAMP-2 antibody levels in the perinuclear ANCA (P-ANCA) group were significantly elevated compared with the non-ANCA group (p = 0.0147). We suggest that anti-LAMP-2 antibody could play an important role in the pathogenesis of CPN in the presence of P-ANCA detected by IIF.