Endoxifen (EDX) is an active metabolite of tamoxifen that has been proven effective in the prevention and treatment of estrogen-positive breast cancer; however, oral administration of tamoxifen often causes severe side effects. Here, the topical delivery of EDX is explored using polymeric micelles to achieve localized drug delivery with potentially minimal side effects. EDX is encapsulated into dendron micelles (DM) with various surface groups (-NH2, -COOH, or -Ac) and into cationic liposomes as a control. End-group modification significantly affects the drug loading, where the DM-COOH micelles allow the most efficient encapsulation. Furthermore, unlike the burst release from the liposomes, all DMs show sustained release of EDX over 6 days. Each formulation is evaluated for its potential to deliver EDX across the skin layers. DMs substantially enhance the permeation of EDX through both mouse (up to 20-fold) and human (up to 4-fold) skin samples relative to ethanol, a chemical penetration enhancer. Franz diffusion cell experiments reveal that DM-COOH induces the highest flux of EDX among all groups. The enhanced drug loading, controlled release profiles, and enhanced skin permeation all demonstrate that DMs are a useful platform for the topical delivery of EDX, offering a potential alternative administration route for chemoprevention.