I was interested to read the paper by Acs B and colleagues published in the Jun 2016 issue of Diagn Cytopathol. They aimed to assess the diagnostic accuracy of ancillary tests applied to fine-needle aspiration cytology (FNAB) in breast tumors and metastases, as a favorable first choice. The authors compared ER and Her2 immunocytochemical (ICC) as well as immunohistochemical (IHC) staining and HER2 fluorescence in situ hybridization (FISH). 1 First of all, reliability (precision) and validity (accuracy) are two completely different methodological issues which should not be confused. (Title of the paper and the aim of the authors indicate to this confusion). They reported that significant difference (P < 0.001) and moderate correlation (j 5 0.44) were noted between results of 97 paired ICC an IHC reactions for ER expression. 1 Considering large sample size, statistically significant (P value < 0.001) differences can easily be obtained; however, clinically importance of the observed difference should be taking into account instead of statistically significant. Moreover, for qualitative variables, weighted kappa should be used. It is crucial to know that simple kappa has two important limitations as below. It depends on the prevalence of each cell (concordant and discordant cells) as well as the number of the categories (the higher the categories, the lower our kappa value. [2][3][4][5][6][7][8] As the authors pointed out in their conclusion, FISH performed on FNAB samples is suitable to categorize primary and metastatic breast cancer in regard of HER2 gene amplification status and can be used as a predictive test in respect of therapies targeting HER2. For prediction, we need two cohort dataset otherwise, we should split one cohort dataset to develop and validate our model. It means without validation, we cannot generalize our results. 2-8 Therefore, such a conclusion can be a misleading message and misdiagnosis as well as mismanagement of the patients cannot be avoided. References 1. Acs B, Szekely N, Szasz AM et al. Reliability of immunocytochemistry and fluorescence in situ hybridization on fine-needle aspiration cytology samples of breast cancers: A comparative study.