Multiple endocrine neoplasia (MEN) syndromes are characterized by the association of various endocrine neoplasias. Prophylactic thyroidectomy is the treatment of choice for patients with RET gene mutations. The age at which patients undergo prophylactic thyroidectomy may vary depending on the position of the RET gene codon. In cases of MEN 2B, when the mutation is carried in codons 883, 918 or 922, prophylactic thyroidectomy is performed prior to 6 months of age, due to the increased aggressiveness of these heterozygosities, which are capable of determining the onset of medullary cancer during the first months of life. We present two heterozygous twin patients with MEN 2B syndrome who were born 32 weeks premature, and who underwent prophylactic thyroidectomy at 7 months of age. The patients were carriers of the mutation at codon 918. We suggested the early surgery at 7 months as, due to their prematurity, the patients were required to gain weight to improve their condition prior to surgery. The two patients had medullary thyroid carcinoma without lymph node involvement. In conclusion, for a truly prophylactic thyroidectomy, such patients should undergo surgery within the first month of life, particularly if these patients are carriers of the mutation in codons 883, 918 or 922.