The RET proto-oncogene encodes a tyrosine-kinase receptor specifically expressed in tissues of neuroectodermal origin. Recently specific point mutations of RET have been demonstrated to be responsible for the Multiple Endocrine Neoplasia type 2A and 2B and Familial Medullary Thyroid Carcinoma syndromes, characterized by the occurrence of medullary thyroid carcinomas. Here we report that a human medullary thyroid carcinoma cell line, the TT cell line, harbours a MEN2A-type mutation, specifically a cysteine to triptophan substitution at the level of the RET codon 634. This mutation is heterozygous and both normal and mutated alleles are expressed. We suggest that the TT cell line could be a useful cell system to investigate the role played by the RET oncogene in the transformation and differentiation of human thyroid C-cells.