Medullary thyroid carcinoma (MTC) is a rare form of neuroendocrine malignancy. Of all thyroid neoplasms MTC accounts for 5%. Tumors develop from the thyroid C-cells which produce calcitonin. Unfortunately, metastatic spread is common in this disease and is linked to increased morbidity and mortality. About 75% of MTC tumors occur sporadic and the rest are part of a hereditary syndrome, usually MEN2A, MEN2B and FMTC. Hereditary MTC are most often caused by mutations in the RET gene. Depending on which amino acid that is affected the clinical phenotype varies. Like in hereditary disease most sporadic MTC carry mutations in RET with other mutations in RAS oncogenes in approximately 20-30%. None have previously investigated genetic heterogeneity using next generation sequencing. Tumor heterogeneity has been studied in multiple tumor types. Using high throughput techniques, it is possible to study the evolution of a tumor. Using whole genome sequencing, RNA sequencing and methylation arrays we have been able to develop an infrastructure to analyze tumor heterogeneity using multiple samples gathered from a patient. This has been used on one cohort of pancreatic neuroendocrine tumors and one cohort of adrenocortical carcinomas. Our plan is to use a similar infrastructure to analyze multiple samples from patients with MTC. In our biobank we have identified ten patients with a total of 18 tumors having primary and metastatic MTCs. Also, we have one patient with a syndromic MTC with both a primary and metastatic tumor. We plan to perform WGS on all samples 60X (n=21) and germline DNA 30X (n=9). RNA sequencing on 21 samples with a minimum of 45milion reads/sample and Methylation array using the Illumina infinium array.