Prostate cancer is the most commonly occurring malignancy and the second-leading cause of cancer-related death in men in the US. The Prostate Specific Membrane Antigen (PSMA) is over-expressed on the surface of prostate cancer cells and has been exploited for targeting the malignant prostate tissue. While quantum dots (QDs) have attracted significant attention in imaging tissues in vivo and cells in vitro, few studies elucidate the intracellular processing of these nanoparticles. We report the differential intracellular sorting and localization of unconjugated fluorescent quantum dots in prostate cancer cells expressing PSMA versus those that do not express the receptor. Quantum dots showed a characteristic punctuated lysozomal intracellular distribution PSMA-negative PC3 cells. However, QDs localized to a single location in the perinuclear region in PSMA-expressing PC3-PIP cells (PC3-PIP cells are derived from PC3 cells following retroviral transduction of the latter with the gene for the PSMA receptor). PSMA is highly homologous to the transferrin receptor and is known to co-localize with transferrin in the recycling endosomal compartment (REC) upon internalization through clathrin-coated pits. Fluorescence microscopy revealed that quantum dots co-localized with transferrin indicating sequestration of these nanoparticles to the REC which is used by cells to recycle receptors back to the surface. Kinetic experiments indicated that the localization of the quantum dots to REC was completed 2-5h post incubation in a dose-dependent fashion. Competitive inhibition experiments with a PSMA-binding antibody resulted in significantly reduced uptake of quantum dots by PC3-PIP cells. Taken together, our results indicate that PSMA plays a role in the differential sorting of nanoparticles via hitherto unknown mechanisms adding another component to the intriguing multidimensionality of the receptor. These results not only set the stage for further investigation into the role of the PSMA receptor in intracellular sorting, trafficking, and recycling, but also have implications in nanoparticle-mediated targeting for prostate cancer drug delivery and imaging.