Melanosomes are specialized melanin-synthesizing organelles critical for photoprotection in the skin. Melanosome transfer to keratinocytes, which involves whole organelle donation to another cell, is a unique biological process and is poorly understood. Time-lapse digital movies and electron microscopy show that filopodia from melanocyte dendrites serve as conduits for melanosome transfer to keratinocytes. Cdc42, a small GTP-binding protein, is known to mediate filopodia formation. Melanosome-enriched fractions isolated from human melanocytes expressed the Cdc42 effector proteins PAK1 and N-WASP by western blotting. Expression of constitutively active Cdc42 (Cdc42(V12)) in melanocytes co-cultured with keratinocytes induced a highly dendritic phenotype with extensive contacts between melanocytes and keratinocytes through filopodia, many of which contained melanosomes. These results suggest a unique role for filopodia in organelle transport and, in combination with our previous work showing the presence of SNARE proteins and rab3a on melanosomes, suggest a novel model system for melanosome transfer to keratinocytes.