Early detection of malignant tumors is vital for improving therapeutic outcomes and patient survival. This comprehensive review evaluates a wide array of early biomarkers—spanning metabolic products, gene activity derivatives, and biochemical indicators—that signal the initiation, promotion, and progression of cancer. Specifically, we spotlight 20 substances, including oncometabolites (e.g., 2-hydroxyglutarate), oxidative damage markers (e.g., 8-hydroxydeoxyguanosine), cancer-testis antigens (e.g., MAGE-A and NY-ESO-1), oncogenic fusion proteins (e.g., BCR-ABL), viral oncogenes (e.g., HPV E6/E7), and antioxidant enzymes. Additionally, alterations in membrane potential, ion channel activity, and circadian-regulated substances such as melatonin further delineate early tumor behavior. A multi-biomarker screening approach was assessed in 1700 ostensibly healthy individuals. Elevations in at least 17 of 20 biomarkers identified 11 high-risk participants, all confirmed by imaging and endoscopic techniques to have early-stage malignancies, including cancers of the lung, breast, stomach, colon, pancreas, and liver. Surgical treatment of these early lesions yielded favorable prognoses, underscoring the potential impact of timely intervention. The review also discusses epigenetic risk factors (e.g., smoking, excessive alcohol use, certain infections) and suggests that integrating biomarker analysis with lifestyle modifications can bolster cancer prevention. Despite the relatively small number of confirmed malignancies, these findings highlight the promise of a multi-biomarker panel for early tumor detection in routine medical evaluations. Future research avenues include refining biomarker panels, enhancing genetic testing integration, and conducting larger, longitudinal studies to validate this approach. Overall, early biomarker screening represents a transformative strategy for reducing cancer mortality by enabling prompt and personalized intervention.