[(99m)Tc]DTPA-mannosyl-dextran is a receptor-binding radiopharmaceutical specifically designed for sentinel lymph node mapping. The purpose of this study was to test the biodistribution and safety of [(99m)Tc]DTPA-mannosyl-Dextran at different molar doses. Twenty-four female breast cancer patients participated in this study. Four groups of 6 patients received an injection of 0.2, 1.0, or 5.0 nmol of [(99m)Tc]DTPA-mannosyl-Dextran or filtered [(99m)Tc]sulfur colloid. The injection site clearance was monitored by dynamic imaging for three hours. Whole body scans were acquired at 2.5 and 12, and lymph nodes were assayed for radioactivity after gamma-guided sentinel lymph node biopsy. Injection site clearance of [(99m)Tc]DTPA-mannosyl-Dextran was not statistically different in a dose-dependent manner. Dose-dependent sentinel node uptake was observed (p = 0.03). There were no clinically significant alterations in laboratory parameters among all dose levels at 4 h or 24 h post injection compared to preoperative levels. Radiation absorbed doses did not differ among the three dose levels, but were lower than filtered [(99m)Tc]sulfur colloid.