The widespread use of mammographic breast screening and the introduction of even more sensitive radiological techniques have placed increasing demands upon the pathologist for the accurate diagnosis and histological categorisation of screen-detected lesions. Subsequent management algorithms rely on correct pathological classification. Needle core biopsy (NCB) has become the mainstay of non-operative diagnosis in many Breast Units. However, despite good specificity and sensitivity, there remain lesions that are particularly challenging on NCB. This may be because they can mimic invasive carcinoma or because there is a risk of associated carcinoma. Particular areas of difficulty arise as a result of the focal nature of sampling inherent with biopsy specimens. Troublesome lesions include atypical epithelial proliferations, sclerosing lesions and radial scars, papillary, columnar cell and apocrine lesions and lobular in situ neoplasia. Immunohistochemistry can be helpful in clarifying the nature of some of these lesions in NCB material but subsequent management nevertheless often remains controversial. Finally, special type invasive carcinomas such as lobular and metaplastic cancers and non-primary malignancies such as lymphoma and metastasis can be misdiagnosed in the limited material of a NCB, particularly if not considered in the differential diagnosis. Good communication between clinician, radiologist and pathologist is especially important in the breast screening setting, in order to avoid misdiagnosis, ensure correct categorisation of NCB samples and to ensure optimum patient care.