BACKGROUNDThe diagnosis of breast lesions is usually confirmed by fine-needle aspiration cytology (FNAC) or histological biopsy. Although there is increasing literature regarding the advantages and limitations of both modalities, there is no literature regarding the accuracy of these modalities for diagnosing breast lesions in high-risk patients, who usually have lesions detected by screening. The objective of the current study was to evaluate diagnostic performance indices of FNAC in breast cancer susceptibility gene (BRCA) mutation carriers. METHODSBRCA1/BRCA2 mutation carriers who underwent FNAC were selected from the database of the Rotterdam Family Cancer Clinic. FNAC accuracy parameters were calculated by taking the outcome of a subsequent histological diagnosis or clinical follow-up as reference standard. RESULTSIn total, 320 FNACs were obtained, and FNAC examination was followed by histological examination in 150 patients. The rate of insufficient material was 25.6%. Sensitivity was 92.3%, specificity 96.3%. The false-positive rate was 3.7%, the false-negative rate was 7.7%, and accuracy was 94.7%. A substantial proportion of patients (35%) with malignant FNAC results underwent histological biopsy upfront surgical resection. Small lesion size (1 cm) and nonpalpability of the breast lesion were a CONCLUSIONSThere is a role for FNAC in diagnosing breast lesions of BRCA1/BRCA2 mutation carriers, ie, to confirm a radiological (probably) benign lesion. However, despite the high overall sensitivity of FNAC, the authors recommend histological biopsy as the preferred diagnostic method for high-risk patients who have small or nonpalpable lesions. Cancer (Cancer Cytopathol) 2013;121:561-567. (c) 2013 American Cancer Society. There is a role for fine-needle aspiration cytology in diagnosing breast lesions from BRCA1/BRCA2 mutation carriers, ie, to confirm a radiological (probably) benign lesion. However, despite the high overall sensitivity of fine-needle aspiration cytology, the authors recommend histological biopsy as the preferred diagnostic method in high-risk patients with small or nonpalpable lesions.