Clinical complexity (CC) is an increasingly recognized feature of internal medicine patients who are often characterized by complex needs determined by both biological (i.e. intrinsic to the patient or disease biology) and non-biological (i.e. socioeconomic, cultural, environmental, behavioural) factors. Breast cancer, one of the most common malignancies worldwide, certainly represents an example of a complex disease. Nonetheless, the concept itself of CC and its possible determinants in breast cancer have been poorly addressed. We herein provide our view about the possible factors triggering CC, the key issues of CC and the related unmet needs in breast cancer.