Simple SummaryThe lymphatic system is an essential component of the human circulatory system that plays a critical role in antigen presentation, mounting immune reactions, gastrointestinal tract lipid absorption, and maintenance of interstitial homeostasis. This complex network of specially adapted vessels and lymphoid organs also represents major pathway for cancer spread. Knowledge of lymphatic anatomy, physiology, and expected imaging appearances is crucial in understanding the pattern of cancer spread, with great implications for treatment and management. In this review article, we discuss lymphatic anatomy, physiology, imaging techniques, and radiographic appearances of cancer spread with relevant illustrative cases.The lymphatic system is an anatomically complex vascular network that is responsible for interstitial fluid homeostasis, transport of large interstitial particles and cells, immunity, and lipid absorption in the gastrointestinal tract. This network of specially adapted vessels and lymphoid tissue provides a major pathway for metastatic spread. Many malignancies produce vascular endothelial factors that induce tumoral and peritumoral lymphangiogenesis, increasing the likelihood for lymphatic spread. Radiologic evaluation for disease staging is the cornerstone of oncologic patient treatment and management. Multiple imaging modalities are available to access both local and distant metastasis. In this manuscript, we review the anatomy, physiology, and imaging of the lymphatic system.