The chromatin-associated Polycomb group (PcG) proteins were first identified in genetic screens for homeotic transformations in Drosophila melanogaster. Besides body patterning, members of the PcG are now known to regulate epigenetic cellular memory, stem cell self-renewal, and cancer development. Here, we discuss the multifarious functions of the PcG family, isoforms of protein complexes, and its enzymatic activities, for example histone methylation, links to DNA methylation, its phosphorylation status, H2A mono-ubiquitination, SUMOylation, and links to non-coding RNA. We also discuss the function of cytosolic PcG complexes as a regulator of receptor-induced actin polymerization and proliferation in a methylation-dependent manner. We propose that the functional versatility of PcG protein complexes contributed significantly to the complexity of heritable gene repression mechanisms, signal transduction, and cell proliferation in cancer development.