Thyroid collision tumors (TCTs) are rare pathological findings, representing <1% of thyroid cancers. This study aimed to compare the main pathological features of TCTs containing medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) components with MTC-only tumors and PTC-only tumors. Methods: The retrospective study included 69 cases diagnosed with TCTs (with simultaneous MTC and PTC components), MTC and PTC. All tumors were comparatively assessed for the classical histopathological prognostic features, including a new grading system for MTC. Results: The main component of TCTs had more frequent microscopic extrathyroidal extension (mETE) (p = 0.000), lymphovascular invasion (LVI) (p = 0.000), perineural invasion (PNI) (p = 0.044), and lymph node metastasis (p = 0.042). Additionally, the TCTs’ MTC component presented with more frequent LVI (p = 0.010). Comparing TCTs’ MTC and PTC components with MTC-only tumors and PTC-only tumors revealed that only the TCTs’ MTC components had statistically significant more frequent mETE (p = 0.010) than MTC-only tumors. When applied to the MTC component of TCTs, the pathological parameters of the new grading system of MTC showed no correlations with other microscopic or clinical aspects. Conclusion: Using classical pathological prognostic features, the comparative analysis revealed that the main TCTs’ component was more aggressive than the minor one. Contrary to PTCs, in TCTs, the medullary component was more aggressive than the papillary one, but also more aggressive than MTC-only tumors.