The medical records of 21 patients evaluated for mastocytosis and 2 patients seen for follow-up of known mastocytosis who underwent bilateral iliac crest aspirations and biopsies were reviewed retrospectively to determine whether mastocytosis could be confirmed in each of a patient's biopsy specimens. In 19 cases (83%), each biopsy specimen showed evidence of mastocytosis; however in 4 cases (17%), only 1 of 2 biopsy sites revealed mastocytosis. Compared with the 4 patients with only a unilateral positive biopsy result, the bilateral group had significantly higher urinary excretion of 11beta-prostaglandin F2alpha, higher serum tryptase levels, and higher serum calcitonin values, and a higher percentage had splenomegaly (37% [7/19] vs 0% [0/4]). The 2 groups could not be distinguished by the main initial symptom(s), presence of urticaria pigmentosa, or other laboratory findings (alkaline phosphatase, aspartate transaminase, or hemoglobin concentrations or total WBC, total eosinophil, or platelet counts). Bilateral biopsies might be useful for diagnosing early systemic mastocytosis or detecting minimal bone marrow involvement.