TROP2 is a crucial biomarker for cancer diagnosis and treatment. However, the variations of HER2 expression levels, particularly low and ultra-low expression, are often neglected in medical practice. Deciphering immunohistochemistry (IHC) scoring guidelines that vary across different cancers can be challenging. Dive into the world of HER2 biomarkers and explore the latest advancements in detecting HER2 mutations. Discover how solid and liquid biopsies are revolutionising our understanding of cancer as well as the significance of low and ultra-low expression by IHC, and learn about the best practices in biopsy collection and tissue processing to improve diagnostic accuracy.