The landmark reviews by Hanahan and Weinberg describe a set of ‘acquired capabilities shared by most and perhaps all types of human cancer’ the authors refer to as the ‘hallmarks of cancer’. Here we present data suggesting that modulation of cell-to-cell signalling is likely to be a major additional hallmark that unifies most of these processes. By systematically examining the expression profiles of receptors and ligands in cell lines, primary cells, tumours and normal tissues profiled by the FANTOM5 and TCGA projects we show that cancer cells express significantly fewer ligands and receptors than normal primary cells. We also show that there is a general shift in the repertoires of transcripts encoding proteins from different subcellular localizations. Significantly fewer secreted and plasma membrane proteins and significantly more nuclear proteins are expressed in the cancer state. We go onto confirm this observation using recent publicly available single cell expression profiles from two solid tumours, glioblastoma and melanoma. Single cancer cells express fewer receptors and ligands than cytogenetically normal oligodendrocytes, fibroblasts and endothelial cells from the same tumours. These reduced repertoires in cancer are likely to effect the complex network of cell-to-cell communication in tumours and have major implications in terms of cell surface targeted therapies.