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Nuclear grade, more than any other pathological feature, is strongly associated with the number and pattern of molecular genetic abnormalities in breast cancer cells. Thus, there are two distinct major pathways to the evolution of low\u2010 and high\u2010grade invasive carcinomas: whilst the former consistently show oestrogen receptor (ER) and progesterone receptor (PgR) positivity and 16q loss, the latter are usually ER\/PgR\u2010negative and show Her\u20102 overexpression\/amplification and complex karyotypes. The boundaries between the evolutionary pathways of well\u2010differentiated\/low\u2010grade ductal and lobular carcinomas have been blurred, with changes in E\u2010cadherin expression being one of the few distinguishing features between the two. In addition, lesions long thought to be precursors of breast carcinomas, such as hyperplasia of usual type, are currently considered mere risk indicators, whilst columnar cell lesions are now implicated as non\u2010obligate precursors of atypical ductal hyperplasia (ADH) and well\u2010differentiated ductal carcinoma <jats:italic>in situ<\/jats:italic> (DCIS). However, only through the combination of comprehensive morphological analysis and cutting\u2010edge molecular tools can this knowledge be translated into clinical practice and patient management. Copyright \u00a9 2005 Pathological Society of Great Britain and Ireland. 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