Folate receptors (FRs), membrane-bound proteins that bind specifically to folate with high affinity, are overexpressed by various cancer types and are therefore used as targets for delivery of therapeutic agents. Molecular spherical nucleic acids (MSNAs) are dendritic formulations of oligonucleotides (ONs) that may have advantages over linear parent ONs with respect to delivery properties. Here, we assembled folate-decorated MSNAs, site-specifically radiolabeled them, and then biologically evaluated their effects in mice bearing HCC1954 breast cancer xenograft tumors. The biodistribution of intravenously administered 18F-radiolabeled MSNAs was monitored using positron emission tomography/computed tomography imaging. The results revealed higher accumulation of folate-decorated MSNAs in FR-expressing organs such as the liver, kidney, and spleen, as well as a higher tumor-to-muscle ratio than that observed for MSNAs without the folate decoration. However, the observed increase was statistically significant only for MSNA structures with a PO backbone. The observed selective uptake of folate-decorated MSNAs highlights their potential as targeted delivery vehicles for therapeutic and diagnostic agents in FR-overexpressing cancers.