Urticaria pigmentosa (UP) is the most common form of cutaneous mastocytosis and may be associated with systemic involvement, most often of the bone marrow. The incidence of systemic involvement is not yet well established, however. To address this question, we subjected a group of 30 adults with histologically proved UP to a retrospective study that included history, physical examination, laboratory tests including cytokine measurements, radiologic examinations, and bone marrow biopsies. The most frequently associated clinical symptoms were recurrent flush episodes in 16 of 30 patients, alcohol intolerance in 13, pruritus in 10, and gastrointestinal problems in 11 (recurrent diarrhea, 8 patients; gastritis, 2 patients; and history of peptic ulcer, 1 patient). Of the 30 patients, 18 (60%) had mast cell infiltrates of the bone marrow (nodular type, 10 patients; diffuse interstitial type, 8 patients). Bone marrow involvement was not correlated with massive cutaneous mast cell infiltration, clinically or histologically, or with the incidence of clinical symptoms and associated hematologic disorders. None of the patients had experienced progression of clinical symptoms, skin or organ involvement, or development of hematologic malignant neoplasms since UP was first diagnosed (10 years on average). Urticaria pigmentosa was found associated with mast cell infiltration of the bone marrow in 18 patients (60%). However, bone marrow involvement does not seem to predict adverse clinical course.