Posttranslational modifications of histone proteins (PTHMs) are involved in the regulation of chromatin packaging and gene expression thus affecting cellular homeostasis. Enzymatic machinery that set PTHMs is often deregulated in cancer resulting in altered global patterns of PTHMs in various cancer types. Detection of cancer-related histone marks in biological fluids such as plasma and serum could serve as useful biomarkers in cancer detection, diagnosis and management. Such biomarkers offer many advantages, such as being minimally invasive and easily accessible. Reflecting this, increasing amounts of data on the impact of circulating histone marks are being published. Here we provide a short insight into PTHMs and their potential utility as circulating cancer biomarkers.