Breast core needle biopsy diagnosis and personalized treatment: navigating pitfalls and challenging lesions

Most breast lesions can be diagnosed accurately on core needle biopsy (CNB); however, certain entities remain diagnostically challenging due to limited tissue sampling, morphological overlap with other lesions, unusual immunoprofiles or lack of reliable ancillary markers. These challenges are compounded by modern clinical requirements, particularly the increasing shift towards neoadjuvant therapy (NAT) where a definitive diagnosis is required before surgical excision. Misclassification may have clinically significant consequences, including inappropriate initiation of NAT or undertreatment of aggressive disease. This review provides a structured diagnostic approach to breast lesions that are particularly prone to misinterpretation on CNB. We discuss malignant lesions that should not trigger NAT, while highlighting the diagnostic and reporting pitfalls associated with microinvasive disease, where definitive confirmation of established invasion is often elusive on limited material. Key morphological clues, immunohistochemical strategies and the selective role of molecular testing in resolving differential diagnoses of overlapping and challenging lesions are emphasized. A transparent reporting style that acknowledges uncertainty, together with multidisciplinary collaboration and selective expert consultation, optimizes patient management. The review aims to provide practical guidance, avoid diagnostic pitfalls and promote safe decision-making when dealing with complex breast lesions on limited biopsy material.