TERT promoter mutations (chr5: 1 295 228C>T e chr5: 1 295 250C>T) were recently described in thyroid tumors, with a prevalence ranging 825% in papillary thyroid cancer (PTC). We and others reported that these mutations strongly associate with a poor outcome in differentiated thyroid cancers. Aim of the present study was to further investigate the prognostic role of both TERT promoter (TERTMUT) and BRAFV600E mutations in a larger series of 216 PTCS with a long follow-up (median: 77 months). We also evaluated the possible additive effect on the outcome of the coexistence of the two genetic alterations. Genetic data were obtained by direct sequencing and were correlated with full clinical data. The prevalence of TERTMUT and of BRAFV600E was 12 and 35% respectively. Ten cases (5%) harbored both TERTMUT and BRAFV600E. Cases with a TERTMUT alone, but not those with BRAFV600E alone, were significantly associated with older age at diagnosis and poorer outcome (P=0.04 for both). No differences in the outcome were noted between cases with the TERTMUT alone or with the coexistence of TERTMUT and BRAFV600E. In conclusion, TERT mutations were found to have a 12% prevalence in PTCs and were confirmed to be a major indicator of poor prognosis. On the other hand, BRAFV600E was not associated with the outcome, consistent with data previously obtained in our series. Moreover, the outcome was not different among tumors with isolated TERTMUT and those with coexistent mutations (TERTMUT/BRAFV600E), indicating that BRAFV600E does not confer an additional effect in the disease persistence.