Molecular imaging of breast cancer is increasingly recognized as a valuable tool for optimizing therapeutic interventions. Among potential targets for molecular imaging reporters, Carbonic Anhydrase IX (CAIX) stands out for its overexpression in tumors characterized by large hypoxic areas and aggressive phenotypes. CAIX, a transmembrane glycoprotein involved in pH regulation, displays a unique proteoglycan-like (PG) domain, not present in other isoforms, that could represent a specific target for imaging and therapy. While high sensitivity imaging techniques such as Positron Emission Tomography (PET) and optical imaging have been applied for CAIX targeting, no in vivo study utilizing Magnetic Resonance Imaging (MRI) to target CAIX has yet been reported. Herein, we address this gap by applying CAIX PG-targeting functionalized liposomes in the first in vivo MRI study on a murine model of breast cancer. TS/A cells were subcutaneously injected to generate primary tumors in mice, and targeted liposomes were delivered intravenously after 15 days. Internalization of the targeted liposomes by receptor-mediated endocytosis led to an enhanced MRI signal in the tumor region. Cytoplasmic and endosomal distribution of the liposomes' payload was observed. Conversely, non-functionalized liposomes and liposomes bearing a scrambled peptide, while entering tumor cells in smaller amounts, localized only to endosomes as expected. The findings reported herein suggest that CAIX PG domain-targeting liposomal formulations exploiting receptor-mediated endocytosis can lead to improved diagnostic capabilities and open avenues for targeted therapeutic delivery for the treatment of tumors overexpressing CAIX, particularly breast cancer.