Medullary thyroid cancer (MTC) is a form of thyroid carcinoma which originates from the calcitonin-secreting neuroendocrine parafollicular cells of the thyroid. It accounts for 510% of all thyroid cancers, and it mostly occurs as a sporadic entity (sMTC), but a familial pattern is also possible. Somatic mutations of RET are reported in 2080% of sMTCs. The majority of MTCs harbour a RET M918T-exon 16 mutation. In sporadic MTCs the RET gene is mutated in codon 918, where a methionine is substituted to a threonine. This transformation of RET gene promotes uncontrolled cell proliferation and tumoural development. The objective of this study was to assess the occurrence of MTC and co-occurring RET M918T mutation in the sample of Croatian population. A nonisotopic polymerase chain reaction (PCR) based single strand conformation polymorphism analysis and heteroduplex gel electrophoresis method was used to screen DNA extracted from 34 formaldehyde fixed and paraffin embedded sMTC specimens of the patients for M918T mutation in RET exon 16. Results were compared with the disease phenotype and clinical findings. A germline methionine/threonine point mutation at codon 918 of the RET tyrosine kinase domain was identified in 21 patients (61.7%) (16 females (76.1%) and five males (23.8%), aged 6278 years). The first data about RET M918T mutational status in the sample of Croatian population with MTC shows that the incidence of RET exon 16 mutation is within generally valid limits. However, all subjects with RET M918T mutation had more aggressive phenotype and worse cancer-specific survival. These data should be confirmed on a larger study group in prospective studies in order to determine whether RET M918T mutation contribute to progression of sMTC. All obtained results could serve in selection of patients for RET-inhibitors therapy with vandetanib and cabozantinib and as predictive biomarkers the same therapy.