Abstract Motivation Data transformations are an important step in the analysis of RNA-seq data. Nonetheless, the impact of transformation on the outcome of unsupervised clustering procedures is still unclear. Results Here, we present an Asymmetric Winsorization per-Sample Transformation (AWST), which is robust to data perturbations and removes the need for selecting the most informative genes prior to sample clustering. Our procedure leads to robust and biologically meaningful clusters both in bulk and in single-cell applications. Availability and implementation The AWST method is available at https://github.com/drisso/awst. The code to reproduce the analyses is available at https://github.com/drisso/awst_analysis Supplementary information Supplementary data are available at Bioinformatics online.