Results: Eight of 15 information cases (53 %) showed nonrandom X-chromosome inactivation, or a clonal process. Of the 26 patients for which IgG4 analysis was performed, 14 (54 %) were positive for IgG4-positive plasma cells and all were negative for ALK. Of the 12 patients, for which both clonality analysis and IgG4 analysis were performed, 4 were clonal and IgG4 negative (33 %), 2 were clonal and IgG4 positive (17 %), 2 were nonclonal and IgG4 positive (17 %), and 4 were nonclonal and IgG4 negative (33 %). Conclusion: Our data indicate that a significant proportion (53 %) of idiopathic retroperitoneal fibrosis cases in females is associated with a clonal expansion of fibroblasts. In addition, a subset of idiopathic retroperitoneal fibrosis cases could be classified in the IgG4-related sclerosing disease spectrum. Although a conclusive association with malignancy, urologic disorder, or systemic disease has not been established, often the lesion carries a challenging clinical differential diagnosis that includes malignancy.