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Microdissection and new PCR clonality assays exploiting X\u2010linked polymorphisms, some of which (including <jats:italic>XIST<\/jats:italic>) are expressed in RNA, create investigational opportunities complementary to other molecular analyses, but a reliable <jats:italic>in situ<\/jats:italic> assay of X\u2010inactivation remains desirable. The necessity for stringent controls in clonality analysis is emphasized. While it may be possible to reconcile \u2018pluriclonal\u2019 (oligoclonal or polyclonal) carcinogenesis with widely accepted paradigms of genetic\/epigenetic change and clonal selection in epithelial neoplasia, it deserves critical study as novel carcinogenic mechanisms would be implied. 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