The records of 32 patients with adult-onset urticaria pigmentosa were analyzed to determine if any clinical or pathologic findings could distinguish urticaria pigmentosa associated with systemic mast cell disease from urticaria pigmentosa with no clinical evidence of systemic mast cell disease. Thirteen patients had biopsy-proven systemic mast cell disease, and 19 had no documentation of systemic mast cell disease after at least 20 years of follow-up. Generally, urticaria pigmentosa with systemic mast cell disease could not be differentiated from urticaria pigmentosa with skin involvement only. Although most patients in both groups had mast cells in a perivascular location, four patients had dense infiltrates filling the papillary dermis. Two of these patients had biopsy-proven systemic mast cell disease, and two had clinical symptoms that could have been produced by systemic mast cell disease, although the diagnosis was not proved by biopsy. The presence of dense infiltration by mast cells in urticaria pigmentosa with cytologic atypia may correlate with the presence of systemic mast cell disease.