Developing biomarkers for early cancer diagnosis is a truly complex and challenging task. Certain roadblocks can impede their development and clinical application. Cancer is a highly heterogeneous disease, meaning that it can vary in its molecular and genetic characteristics even within the same type of cancer. Identifying biomarkers that accurately represent this heterogeneity and can be universally applicable is a significant challenge. Many biomarkers may be elevated in various conditions, including non-cancerous diseases. This lack of specificity can lead to falsepositive results and unnecessary follow-up testing or procedures, causing anxiety and increasing healthcare costs. Also, biomarker levels can vary significantly between individuals due to factors such as age, sex, ethnicity, lifestyle, and comorbidities. This variability can make it challenging to establish accurate cutoff values for diagnosis or risk assessment. Achieving both high sensitivity (detecting true positives) and high specificity (avoiding false positives) is often challenging. Biomarkers that are highly sensitive may yield false-positive results, while highly specific biomarkers may miss some cases of cancer.