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Its aggressiveness has been linked to distinct clinicopathological features. Novel pathological predictors of aggressiveness have also been described in the literature. However, these remain contentious, to date. To assess the prognosticators of aggressiveness for MTC and establish potentially novel ones. The primary endpoint was to establish predictors for central and\/or lateral cervical nodal metastatic disease. Whereas secondary endpoints include defining biochemical and histopathologic markers of aggressiveness. A multi-center retrospective analysis of prognosticators of aggressiveness in MTC. 785 patients with MTC were enrolled. The mean age was 56 years with a female to male ratio of 1: 1.7. Regression analysis demonstrated that aggressive prognosticator predictive of nodal metastasis included: age, pre- and post-operative Calcitonin and CEA levels, tumor size, multifocality, capsular and lymphovascular invasion, the presence of extrathyroidal extension, Ki-67, and RET positivity, desmoplasia, and inflammatory scores. This study provides an expanded spectrum of prognosticators of tumor aggressiveness. 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