Antibodies contribute significantly to the reproducibility crisis in life sciences, due to variability in their performance (affinity and specificity). This is especially critical in epigenomics, where antibodies are used to characterise chromatin modifications and regulatory proteins that alter chromatin states and regulate gene expression. These modifications include diverse molecules that are directly covalently bound to DNA (e.g. methylation) or histone proteins (e.g. acetylation), and (re)arrange nucleosomes (e.g. histone chaperones). A recently developed method, Cleavage Under Targets and Tagmentation (CUT&Tag) that utilises antibody guided targeted tagmentation, allows profiling of histone post translational modifications at single cell resolution. However, antibody performance can vary, and results may not align with other assays like ChIP-seq. Using a nucleosome panel consisting of different histone lysine methylation states, I screened the specificity of several commercial antibodies, identifying both high- and low-specificity in CUT&Tag, emphasising the need for assay specific validation.