Medullary thyroid carcinoma (MTC) occurs mostly as a sporadic tumor or in connection with inherited cancer syndromes-multiple endocrine neoplasia (MEN) types 2A and 2B and familial MTC. Germline mutations in the RET proto-oncogene are found in most of the familial cases. Somatic mutations in the RET proto-oncogene are detected in 23%-69% of patients with sporadic MTC. The most frequent somatic mutation is Met918Thr in exon 16 and only a small percentage of mutations in other RET exons have been observed. In a very few cases double mutations were found. Genetic screening for somatic mutations in RET exons 10, 11, 13, 14, 15, and 16 in Czech patients with sporadic MTC was carried out by DNA sequencing. This study presents a new triplesomatic mutation Gly911Asp, Met918Thr, and Glu921Lys in exon 16 of the RET proto-oncogene detected in an 18-year-old Czech male patient. In the second case, a new double-somatic mutation Val591Ile in exon 10 with a concomitant somatic mutation Met918Thr in exon 16 was found in a 77-year-old Czech female patient. These both newly described somatic multiple mutations were revealed in a hemizygous status, the loss of heterozygosity in tumor tissues in comparison with germline DNA was confirmed.