Objective: Gene therapy acts on change of prodrug into cytotoxic drug inside tumor cells transfected by foreign enzyme. It uses also "bystander" effect on surrounding tumor cells without enzyme. We used yeast Cytosine deaminase (yCD) in combination with 5-fluorocytosine (5FC) converted into 5-fluorouracil (5FU) and its metabolites. Medullary thyroid carcinoma (MTC) is a malignant tumor often with therapy resistant distant metastases. Patients with sporadic form have metastases at the time of diagnosis, mostly in bones, lungs and liver. The aim of this study was to evaluate the efficiency of yCD/5FC in MTC treatment using xenotransplants derived from model TT cell line in nude mice. Method: Tumors were immunohistochemically stained with polyclonal antibody anti-EGFP (enhanced green fluorescence protein) and monoclonal antibodies anti-PCNA and anti-Ki67. Positivity was semiquantitatively evaluated. Results: Diffuse positivity for PCNA was seen in untreated and treated tumors, respectively. Positivity for Ki-67 was diffuse in untreated and only sporadic in treated tumors. Conclusion: Diffuse PCNA positivity in treated tumors suggests that the tumor cells stopped in S phase. Scattered positivity of Ki-67 after treatment document suppressed proliferation mediated by yCD/5FC gene therapy, which implies therapeutic application in patients with metastatic MTC. (ITMS 26240220052, VEGA 2/008/11, VEGA 2/0146/10).