Objectives <p>Coexisting medullary and papillary thyroid cancer (MTC–PTC) are rare, and large-scale studies with sufficient sample sizes to delineate its distinct characteristics remain limited.</p> Methods <p>This study included 87 patients pathologically diagnosed with MTC–PTC. For comparison, two additional cohorts consisting of 709 patients with solitary MTC and 1,178 patients with solitary PTC were included. Biological features and survival outcomes were systematically evaluated across patients.</p> Results <p>Compared with solitary MTC, the MTC–PTC cohort had significantly lower preoperative calcitonin, fewer RET mutations and earlier tumor stages in MTC components (all <i>P</i> &lt; 0.05). MTC–PTC cases were further divided into ipsilateral and contralateral groups according to their spatial locations. Compared with both the contralateral and solitary MTC groups, the ipsilateral group consisted exclusively of sporadic MTCs and demonstrated the lowest frequency of RET^M918T mutations, the highest proportion of T1-stage tumors, and the lowest calcitonin levels (all <i>P</i> &lt; 0.05). Multivariable Cox regression also identified the ipsilateral group as an independent predictor of improved structural recurrence–free survival (<i>P</i> &lt; 0.001). PTC lesions in contralateral group exhibited less aggressive features than ipsilateral and solitary PTCs, including lower rates of extrathyroidal extension and multifocality (<i>P</i> = 0.007), lower TGAb levels (<i>P</i> = 0.021), earlier T/N stages.</p> Conclusions <p>This study highlights distinct clinicopathological and survival differences between coexisting and solitary thyroid cancers, as well as between subtypes of MTC–PTC. Further studies with larger cohorts and integrative molecular analyses are warranted to elucidate these mechanisms.</p>