Medullary thyroid cancer (MTC) arises from parafollicular C cells and is an elusive tumor to image. It occurs as a sporadic neoplasm in 70-80% of cases and is hereditary in 20-30% because of germline mutations of the rearranged during transfection proto-oncogene. Successful disease management relies on accurate staging. Tumor secretory biomarkers are highly sensitive to a disease; however, despite a wide variety of radiopharmaceuticals for molecular imaging that take advantage of hybrid SPECT/CT and PET/CT fusion imaging, imaging of MTC is still problematic. After initial surgical resection, the limited sensitivity of localization of small locoregional disease and the inability to detect early liver metastases hamper the success of later surgical approaches. F-fluorodeoxyglucose PET has been used to detect MTC recurrences with modest success and may be best suited for only a small subset of more biologically aggressive MTCs. Recent developments in PET imaging with novel radiopharmaceuticals targeting specific cellular processes of MTC offer increased sensitivity for identifying recurrence, assessing prognosis, and guiding selection of optimal therapies.