Polycomb group (PcG) proteins regulate transcription, playing a key role in stemness and differentiation. Deregulation of PcG members is known to be involved in cancer pathogenesis. Emerging evidence suggests that CBX2, a member of the PcG protein family, is overexpressed in several human tumors, correlating with lower overall survival. Knock-down of CBX2 expression promotes neurite development, while overexpression of CBX2 inhibits neurite development. CBX2 is a direct target gene of miR-124. During neuronal differentiation, CBX2 was decreased while miR-124 was increased. The neuron-specific GAP-43 gene could contribute to the stimulating effect on neurite development associated with inhibition of CBX2. Chromobox 2 (CBX2), a component of polycomb repressive complex 1 (PRC1), binds lysine 27-methylated histone H3 (H3K27me3) via its chromodomain (CD) and plays a critical role in repressing developmentally regulated genes. Cbx2 may present a novel biomarker for predicting the prognosis of breast cancer patients. Cbx2 may also represent a potential target for treatment due to its important function in Taxol treatment responses.