Herein, we describe for the first time the proof-of-concept of CXCR4-directed PET MRI with [68Ga]Pentixafor in response assessment in a patient with extranodal marginal zone lymphoma (MZL) of the orbital cavities and compare it to standard [18F]FDG PET imaging. Here, CXCR4 is linked to marginal zone lymphoma.