RAS mutations (HRAS, NRAS and KRAS) are found in all epithelial thyroid malignancies. The frequency of HRAS mutations in thyroid carcinomas is 4% (COSMIC). While most non-thyroid cancers have mutations in KRAS codons 12 and 13, most thyroid tumors have been found to have mutations in NRAS codon 61 and HRAS codon 61 (Nikiforov 2011).

RAS mutations are identified in 10–20% of papillary carcinomas, 40–50% of follicular carcinomas and 20–40% of poorly differentiated and anaplastic carcinomas (Nikiforov 2011).

Several studies have found RAS mutations to be prevalent in follicular carcinomas, follicular variant papillary carcinomas and poorly differentiated thyroid carcinomas. Ras mutant thyroid cancers are prone to distant metastases to lung and bone rather than to locoregional lymph node involvement.

RAS mutations are the second most common mutation detected in fine-needle aspiration (FNA) biopsy samples from thyroid nodules and have a 74–88% positive predictive value for malignancy (Bhaijee and Nikiforov 2011).

Of note, RAS point mutations are mutually exclusive with other thyroid mutations such as BRAF, RET/PTC, or TRK rearrangements (Kimura et al. 2003) in papillary thyroid cancers . In follicular carcinomas, RAS mutations are mutually exclusive with PAX8-PPARG rearrangements (Nikiforova et al. 2003).

HRAS mutations are also found in ~25% of sporadic medullary thyroid cancers (Moura et al. 2011).