False-positive FNA due to highly sensitive BRAF assay

False-positive BRAF analysis on fine-needle aspiration (FNA) has rarely been reported in the literature but may become more common with the advent of assays that can detect the BRAF V600E mutation in only 2% of otherwise wild-type thyroid cells. We present the case of an indeterminate BRAF-positive FNA that showed no evidence of cancer on final surgical pathology. Case report and literature review. An 87-year-old female with an indeterminate 1.7-cm nodule but BRAF-positive cytology underwent thyroid lobectomy. Final pathology revealed a benign adenomatoid nodule. An area rich in tumor cells from the nodule was identified, labeled, and microdissected for molecular testing, which demonstrated only wild-type BRAF, at the analytical limit of the assay. Increasingly sensitive BRAF assays using dual-priming oligonucleotide-based multiplex polymerase chain reaction analysis can detect the BRAF V600E mutation when present in only 2% of a population of wild-type cells. This increases the risk of false-positive results, particularly in cases of indeterminate FNA. Clinicians must caution patients in these circumstances that BRAF molecular testing may not have a 100% positive predictive value.