The term thyroid tumours of uncertain malignant potential (TT-UMP) has been proposed for a subgroup of follicular-patterned thyroid tumours for which benignancy or malignancy cannot be assessed with certainty. The frequency, diagnostic reproducibility, immunohistochemistry and molecular genetic profiling of such tumours have been poorly explored. We, therefore, investigated (1) the frequency of TT-UMP diagnosed in a single institution (Nice, France: 2004-2008), (2) the observer variation among four pathologists, (3) whether immunohistochemical and molecular genetic profiling of TT-UMP provide additional information concerning such lesions. A series of 31 diagnosed TT-UMP (2.9%) out of 1,078 consecutive thyroidectomies were analysed. It comprised 15 follicular thyroid tumours of UMP (FT-UMP) and 16 well-differentiated tumours of UMP (WDT-UMP). Observer concordance was 70% for all TT-UMP. More than 50% of FT-UMP expressed galectin-3 and CK19, whereas more than 50% of WDT-UMP expressed HBME-1. Five cases of TT-UMP showed N-RAS mutations, while one showed H-RAS mutation and another PAX8/PPARgamma rearrangement. In conclusion, the frequency of TT-UMP is low in our institution. Diagnostic reproducibility is within the same range as other published data on follicular-patterned thyroid tumours. The ancillary methods have a low impact on aiding diagnosis of such lesions.