B-RAF V600E mutation is frequently observed in several tumors, including papillary thyroid carcinomas (PTCs), where it is considered of potential diagnostic and prognostic value. The reported prevalence of B-RAF mutation in PTCs in different Italian populations varies from 14% to 69%. The authors investigate the prevalence and utility of the B-RAF V600E mutation in a series of 91 fine needle aspiration biopsies (FNABs) of the thyroid and in 60 histologically proven PTCs in a well-defined north Italian population. In their series, the B-RAF mutation was detected in 43 (72%) PTCs and was more frequent in classic (34 out of 44, 77%) versus variant follicular PTCs (PTCVF; 9 out of 16, 56%). In all, 41 (46%) FNABs showed B-RAF mutation and corresponded to histologically proven PTCs (33 classic type and 8 PTCVF), which had been cytologically classified as malignant (28 cases), atypical/suspicious (10), inadequate (1), and benign (2). B-RAF mutations were never seen in non-PTC/ PTCVF FNAB cases, implying a 100% positive predictive value.These data demonstrate a high prevalence of B-RAF mutations in the present study population, underscoring the possibility of strong regional differences in B-RAF mutation prevalence in PTCs and further confirming its high diagnostic value on FNAB.