In patients with human epidermal growth factor receptor 2 (HER2)-low breast cancer, the molecular classification of their case plays a pivotal role in the formulation of personalized treatment plans aimed at optimizing outcomes. Despite notable advancements in this field, significant challenges persist. Issues such as pre-analytical variability, interpretative ambiguity, and inconsistent threshold definitions hinder accurate diagnosis and subsequent treatment decisions. In this context, emerging liquid biopsy technologies present a promising solution.