We obtained activated ret cDNAs (retTPC) from a human papillary thyroid carcinoma cell line, TPC-1, and characterized its structure. The nucleotide sequence indicated that the recombination had occurred just upstream of the kinase domain of ret proto-oncogene and that the position, where the conserved sequence of ret proto-oncogene starts in retTPC transcripts, was exactly the same as that of ret-II which we have previously analyzed. Furthermore, a unique 13-glycine stretch, which is also present in a small subunit of the calcium dependent protease, calpain, was detected in the replaced sequence of retTPC. The aberrant tyrosine kinase activity induced by the rearrangement of ret proto-oncogene could be involved in the development of papillary thyroid carcinoma.