Medullary thyroid carcinoma (MTC) is a rare neuroendocrine cancer originating from parafollicular C-cells that produce calcitonin, and accounts for 2%-3% of all thyroid carcinomas. Sporadic forms represent 70% of cases and inherited forms (autosomal dominant) account for 30% of cases, often occurring in younger patients, and can be associated with MEN syndromes.1 Despite well-established criteria for the diagnosis of MTC, the cytological diagnosis can often be challenging2,3 and mutational analysis can serve as an important adjunct. The RET proto-oncogene and overexpression of miR-375 have been previously reported in association with MTC.4,5 However, RAS mutations can also be present in some MTC cases,6 are common to non-malignant thyroid disease, and can also show lack of detectable oncogenic mutational change. Here, we evaluated NGS mutational analysis, including RET proto-oncogene and 14 RET fusions transcripts, combined with microRNA expression profiling (Table 1) for the classification of MTC relative to other thyroid malignancies and benign lesions. Our analysis clearly demonstrates that MTCs show overexpression of miR-375 with or without the presence of RET mutations.