Purpose: 99mTc-tilmanocept is the first mannose-containing, receptor-directed, radiopharmaceutical for molecular imaging and mapping of sentinel lymph nodes (SLNs) in solid tumor staging. This review focuses on the approved and innovative clinical application of 99mTc-tilmanocept. Results and conclusion: 99mTc-Tilmanocept is a new-generation radiotracer designed to overcome certain limitations of the conventionally used radiocolloids. The superior efficacy profile of 99mTc-tilmanocept has been demonstrated in several preclinical and clinical studies based on its specific properties like rapid injection site clearance, high uptake in the first node, and low distal node accumulation. The capability of 99mTc-tilmanocept for selective molecular imaging of the CD206 receptor may be used for diagnosis and treatment of several macrophage mediated diseases, including autoimmune diseases, infectious diseases (HIV and tuberculosis), neurodegenerative disorders (dementias) and cardiovascular disease (vulnerable plaque and atherosclerosis).